Limited-angle TOF-PET for intraoperative surgical applications: proof of concept and first experimental data

The intraoperative gamma probe (IPG) based on single gamma-ray detection remains the current gold standard modality for sentinel lymph node identification and tumor removal in cancer patients. However, IPGs do not meet the <5% false negative rate (FNR) requirement, a key metric suggested by the American Society of Clinical Oncology (ASCO). We aim to reduce FNR by using time of flight (TOF) PET detector technology in limited angle geometry system by using only two detector panels in coincidence. For proof of concept, we used two Hamamatsu TOF PET detector modules (C13500-4075YC-12) featuring 12× 12 arrays of 4.14× 4.14× 20 mm3 LFS crystal pixels with 4.2 mm pitch and coupled one-one to silicon photomultiplier (SiPM) pixels. The measured detector coincidence timing resolution (CTR) was 271 ps FWHM for the whole detector. We 3D printed lesion phantom containing spheres 2–10 mm in diameter, representing lymph nodes, and placed it inside a 10-liter warm background water phantom. Experimental results showed that with subminute data acquisition, 6 mm diameter spheres could be identified in the image when a lesion phantom with a 10:1 activity ratio to background was used. The simulation results were in good agreement with the experimental data by resolving 6 mm diameter spherical lesions with a 60 second acquisition time in a 25 cm deep background water phantom with a 10:1 activity ratio. As expected, the image quality improved as the CTR improved in the simulation and with decreasing background water phantom depth or increasing lesion-to-background activity ratio in the experiment. With the results presented here, we concluded that using a limited angle TOF PET detector system is a major step forward for intraoperative applications in that lesion detectability is beyond what conventional gamma- and NIR-based probes could achieve.

Detection of the sentinel lymph node with hybrid tracer (ICG-[99mTc]Tc-albumin nanocolloid) in intermediate- and high-risk endometrial cancer: a feasibility study

Purpose Indocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [99mTc]-based colloids. Hybrid tracers such as ICG-[99mTc]Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC. Methods Fifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera. Results Preoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis was identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%. Conclusion TUMIR injection of a hybrid tracer in patients with intermediate- and high-risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.

Sentinel lymph node identification in early stage ovarian cancer: is it still possible after prior tumor resection?

Objective Sentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy. Methods Patients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-min, the sentinel node(s) were identified using either the gamma-probe and / or blue dye. Results A total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%. Conclusion In this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection. Trial registration NCT02540551

Detection of the Sentinel Lymph Node With Hybrid Tracer (ICG-[99mTc]Tc-albumin Nanocolloid) in Intermediate and High Risk Endometrial Cancer. A Feasibility Study

Purpose: Indocyanine green (ICG) is frequently used for the detection of the sentinel lymph node (SLN) in gynecology, but it carries the loss of the presurgical SLN mapping provided by [99mTc]-based colloids. Hybrid tracers such as ICG-[99mTc] Tc-albumin nanocolloid combine the benefits of both components. The aim of this study was to evaluate the feasibility and applicability of this hybrid tracer injected by transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) approach in the detection of SLNs in patients with intermediate- and high-risk EC. Methods: Fifty-two patients with intermediate- and high-risk EC underwent SLN biopsy after injection of a hybrid tracer using the TUMIR approach, followed by pelvic and paraaortic lymphadenectomy. SLNs were detected preoperatively by lymphoscintigraphic study and intraoperatively by gamma probe and near-infrared (NIR) optical laparoscopic camera. Results: Preoperative lymphatic drainage was obtained in 69% and intraoperative detection in 71.4% of patients. A total of 146 SLNs (4.17 SLNs/patient) were biopsied. Pelvic bilateral detection was observed in 57% of the women and paraaortic drainage in 34% of the patients. The radioactive component allowed the detection of SLN in 97.1% of the patients, while the fluorescent component detected 80%. In more than 17% of the patients with intraoperative detection, SLNs were detected only by the radioactive signal. Lymph node metastasis were identified in 14.3% of patients submitted to SLNB. The sensitivity and negative predictive value for metastatic involvement were 100%. Conclusion: TUMIR injection of a hybrid tracer in patients with intermediate- and high- risk EC combines the benefits of the radiotracer and the fluorescence methods with a single tracer. The method increases the paraaortic detection rate and allows a potential increase in SLN detection. Notwithstanding, based on our findings, the radioactive component of the hybrid tracer cannot be obviated.

Introducing the GammaPen: All-in-One Gamma Probe for Sentinel Lymph Node Biopsy

Purpose: Using an itra-operative gamma probe after injection of radiotracer during surgery helps the surgeon to identify the sentinel lymph node of regional metastasis through the detection of radiation. This work reports the design and specification of an integrated gamma probe (GammaPen), developed by our company. Materials and Methods: GammaPen is a compact and fully integrated gamma probe. The detector module consists of a thallium-activated Cesium Iodide (CsI (Tl)) scintillator, and a Silicon Photo Multiplier (SiPM), shielded using Tungsten housing. Probe sensitivity, spatial resolution and angular resolution in air and water, and side and back shielding effectiveness were measured to evaluate the performance of the probe based on NEMA NU3 standard. Results: The sensitivity of the probe in the air/water at distances of 10, 30, and 50 mm is 18784/176800, 3500/3050, and 1575/1104 cps/MBq. The spatial and angular resolutions in the air/scattering medium are 40/47 mm and 77/87 degrees at a 30 mm distance from the probe. The detector shielding effectiveness and leakage sensitivity are 99.91% and 0.09%, respectively. Conclusion: The results and surgeon experience in the operating room showed that GammaPen can be effectively used for sentinel lymph node localization.

The Click-On gamma probe, a second-generation tethered robotic gamma probe that improves dexterity and surgical decision-making

Purpose Decision-making and dexterity, features that become increasingly relevant in (robot-assisted) minimally invasive surgery, are considered key components in improving the surgical accuracy. Recently, DROP-IN gamma probes were introduced to facilitate radioguided robotic surgery. We now studied if robotic DROP-IN radioguidance can be further improved using tethered Click-On designs that integrate gamma detection onto the robotic instruments themselves. Methods Using computer-assisted drawing software, 3D printing and precision machining, we created a Click-On probe containing two press-fit connections and an additional grasping moiety for a ProGrasp instrument combined with fiducials that could be video tracked using the Firefly laparoscope. Using a dexterity phantom, the duration of the specific tasks and the path traveled could be compared between use of the Click-On or DROP-IN probe. To study the impact on surgical decision-making, we performed a blinded study, in porcine models, wherein surgeons had to identify a hidden 57Co-source using either palpation or Click-On radioguidance. Results When assembled onto a ProGrasp instrument, while preserving grasping function and rotational freedom, the fully functional prototype could be inserted through a 12-mm trocar. In dexterity assessments, the Click-On provided a 40% reduction in movements compared to the DROP-IN, which converted into a reduction in time, path length, and increase in straightness index. Radioguidance also improved decision-making; task-completion rate increased by 60%, procedural time was reduced, and movements became more focused. Conclusion The Click-On gamma probe provides a step toward full integration of radioguidance in minimal invasive surgery. The value of this concept was underlined by its impact on surgical dexterity and decision-making.