An in vitro study for the dosimetric and radiobiological validation of respiratory gating in conventional and hypofractionated radiotherapy of the lung: effect of dose, dose rate, and breathing pattern.

Stereotactic body radiotherapy (SBRT) of the lung has become a standard of care for early-stage inoperable non-small cell lung cancer (NSCLC). A common strategy to manage respiratory motion is gating, which inevitably results in an increase in treatment time, especially in irregularly-breathing patients. Flattening-filter free (FFF) beams allow for delivery of the treatment at a higher dose rate, therefore counteracting the lengthened treatment time due to frequent interruption of the beam during gated radiotherapy. In this study, we perform our in vitro evaluation of the dosimetric and radiobiological effect of gated lung SBRT with simultaneous integrated boost (SIB) using both flattened and FFF beams. A moving thorax-shaped phantom with inserts and applicators was used for simulation, planning, gated treatment delivery measurements and in vitro tests. The effects of gating window, dose rate, and breathing pattern were evaluated. Planned doses represented a typical conventional fractionation, 200 cGy per fraction with SIB to 240 cGy, flattened beam only, and SBRT, 800 cGy with SIB to 900 cGy, flattened and FFF beams. Ideal, as well as regular and irregular patient-specific breathing patterns with and without gating were used. A survival assay for lung adenocarcinoma A549 cell line was performed. Delivered dose was within 6% for locations planned to receive 200 and 800 cGy and within 4% for SIB locations. Time between first beam-on and last beam-off varied from approximately 1.5 min for conventional fractionation, 200/240 cGy, to 10.5 min for gated SBRT, 800/900 cGy doses, flattened beam and irregular breathing motion pattern. With FFF beams dose delivery time was shorter by a factor of 2-3, depending on the gating window and breathing pattern. We have found that, for the most part, survival depended on dose and not on dose rate, gating window, or breathing regularity.

Using simultaneous PET/MRI to compare the accuracy of diagnosing frontotemporal dementia by arterial spin labelling MRI and FDG-PET.

PURPOSE: The clinical utility of FDG-PET in diagnosing frontotemporal dementia (FTD) has been well demonstrated over the past decades. On the contrary, the diagnostic value of arterial spin labelling (ASL) MRI - a relatively new technique - in clinical diagnosis of FTD has yet to be confirmed. Using simultaneous PET/MRI, we evaluated the diagnostic performance of ASL in identifying pathological abnormalities in FTD (FTD) to determine whether ASL can provide similar diagnostic value as FDG-PET. METHODS: ASL and FDG-PET images were compared in 10 patients with FTD and 10 healthy older adults. Qualitative and quantitative measures of diagnostic equivalency were used to determine the diagnostic utility of ASL compared to FDG-PET. Sensitivity, specificity, and inter-rater reliability were calculated for each modality from scores of subjective visual ratings and from analysis of regional mean values in thirteen a priori regions of interest (ROI). To determine the extent of concordance between modalities in each patient, individual statistical maps generated from comparison of each patient to controls were compared between modalities using the Jaccard similarity index (JI). RESULTS: Visual assessments revealed lower sensitivity, specificity and inter-rater reliability for ASL (66.67%/62.12%/0.2) compared to FDG-PET (88.43%/90.91%/0.61). Across all regions, ASL performed lower than FDG-PET in discriminating patients from controls (areas under the receiver operating curve: ASL = 0.75 and FDG-PET = 0.87). In all patients, ASL identified patterns of reduced perfusion consistent with FTD, but areas of hypometabolism exceeded hypoperfused areas (group-mean JI = 0.30 ± 0.22). CONCLUSION: This pilot study demonstrated that ASL can detect similar spatial patterns of abnormalities in individual FTD patients compared to FDG-PET, but its sensitivity and specificity for discriminant diagnosis of a patient from healthy individuals remained unmatched to FDG-PET. Further studies at the individual level are required to confirm the clinical role of ASL in FTD management.

A novel 3D-printed phantom insert for 4D PET/CT imaging and simultaneous integrated boost radiotherapy.

PURPOSE: To construct a 3D-printed phantom insert designed to mimic the variable PET tracer uptake seen in lung tumor volumes and a matching dosimetric insert to be used in simultaneous integrated boost (SIB) phantom studies, and to evaluate the design through end-to-end tests. METHODS: A set of phantom inserts was designed and manufactured for a realistic representation of gated radiotherapy steps from 4D PET/CT scanning to dose delivery. A cylindrical phantom (φ80 × 120 mm) holds inserts for PET/CT scanning. The novel 3D printed insert dedicated to 4D PET/CT mimics high PET tracer uptake in the core and low uptake in the periphery. This insert is a variable density porous cylinder (φ44.5 × 70.0 mm), ABS-P430 thermoplastic, 3D printed by fused deposition modeling an inner (φ11 × 42 mm) cylindrical void. The square pores (1.8 × 1.8 mm2 each) fill 50% of outer volume, resulting in a 2:1 PET tracer concentration ratio in the void volume with respect to porous volume. A matching cylindrical phantom insert is dedicated to validate gated radiotherapy. It contains eight peripheral holes and one central hole, matching the location of the porous part and the void part of the 3D printed insert, respectively. These holes accommodate adaptors for Farmer-type ion chamber and cells vials. End-to-end tests were designed for imaging, planning, and dose measurements. RESULTS: End-to-end test were performed from 4D PET/CT scanning to transferring data to the planning system, target volume delineation, and dose measurements. 4D PET/CT scans were acquired of the phantom at different respiratory motion patterns and gating windows. A measured 2:1 18F-FDG concentration ratio between inner void and outer porous volume matched the 3D printed design. Measured dose in the dosimetric insert agreed well with planned dose on the imaging insert, within 3% for the static phantom and within 5% for most breathing patterns. CONCLUSIONS: The novel 3D printed phantom insert mimics variable PET tracer uptake typical of tumors. Obtained 4D PET/CT scans are suitable for segmentation and treatment planning and delivery in SIB gated treatments. Our experiments demonstrate the feasibility of this set of phantom inserts serving as end-to-end quality-assurance phantoms of SIB radiotherapy.

Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model.

Sentinel lymph node (SLN) identification with preoperative image guidance may improve pathological staging of prostate cancer by identifying nodes outside the standard template of dissection. Four anesthetized male dogs received an intra-prostatic injection of Ga-68-labeled tilmanocept. Every 20 min the pelvic lymph nodes were imaged using PET/CT fusion imaging. At 90 min post-injection a prostatectomy and extended lymphadenectomy were completed; ex vivo radioactivity was recorded for each node using a handheld gamma detector, and confirmed by calculation of percent-of-injected dose (%ID) via assay of Ga-68 radioactivity. SLNs were defined as containing >10 % of the maximum %ID. Preoperative PET/CT fusion imaging identified a mean of 4.25 lymph nodes per animal (range 3-7); the mean number of SLN per animal was 4.00 (range 2-6).Of the excised SLNs, 29 % were located in the standard external iliac and obturator distribution. The SLN %ID ranged from 0.07 to 2.40 % (mean 0.744 % ± 0.641 %); SLN ex vivo count rate ranged from 88 to 2,175 cpm (mean 896 ± 715 cpm); and the SLN standardize uptake values (SUVs) ranged from 13 to 237 (mean 79 ± 67).There was a high concordance of PET-CT imaging to SLN activity, with sensitivity of 93 %. In this feasibility study, pelvic SLNs attained SUVs within 60 min. PET/CT effectively identified SLNs with good anatomic specificity, and radioactivity by hand-held detection and scintillation counts demonstrated high concordance with preoperative imaging. Gallium-68-labaled tilmanocept was highly specific for sentinel nodes. Image-guided tumor resection and lymphadenectomy may become a promising future application in urologic oncology and warrants further investigation.

Pediatric gastrointestinal nuclear medicine.

General localization of gastrointestinal bleeding through the use of labeled red blood cells may be performed in children, or (99m)Tc-pertechnetate may be used if a Meckel's diverticulum is suspected. As in adults, cholecystitis and biliary leak may be assessed in children via (99m)Tc-IDA derivatives. Gastroesophageal reflux can be evaluated by oral consumption of the child's usual diet labeled with (99m)Tc sulfur colloid. For the scintigraphic determination of pulmonary aspiration, a relatively high concentration of tracer within a drop of liquid is placed beneath the child's tongue followed by dynamic imaging of the respiratory tract. Colonic transit scintigraphy can aid in the identification and therapeutic decision-making in patients with functional fecal retention, the most common cause of chronic constipation in children. (18)F-DOPA positron emission tomography is useful for classifying pancreatic involvement in infantile hyperinsulinism as focal or diffuse, thereby differentiating between patients who should receive curative focal pancreatic resection versus those who should receive medical management. Assessment of protein-losing enteropathy can be conducted scintigraphically and, compared with fecal alpha-1 antitrypsin collection, the scintigraphic method can detect esophageal and gastric protein loss. Also, scintigraphic quantification of protein loss can be performed without the requirement for fecal collection. Intestinal inflammation in children with inflammatory bowel disease can be evaluated using (99m)Tc white blood cells. The scintigraphic method is safe, accurate, well-tolerated by children and complementary to endoscopy in most patients.