Radiation Exposure from GEP NET Surveillance.

BACKGROUND: Neuroendocrine tumors (NET) are neoplasms that secrete peptides and neuroamines. For gastroenteropancreatic (GEP) NET, surgical resection represents the only curative option. Ten-year imaging surveillance programs are recommended due to long time-to-recurrence following resection. We performed retrospective chart review evaluating radiation exposure and practice patterns from surveillance of completely resected GEP NET. METHODS: We performed a retrospective cohort study of cases with well-differentiated GEP NET from January 2005 to July 2020. Location of primary, modality of imaging, and duration of follow-up were collected. Dosimetry data was collected to calculate effective dose. RESULTS: 62 cases were included with 422 surveillance scans performed. Cross-sectional imaging was used in 82% and functional imaging was used in 18% of scans. Mean number of scans per year was 1.25 (0.42-3). Mean total effective dose was 56.05 mSv (SD 45.56; 0 to 198 mSv) while mean total effective dose per year was 10.62 mSv (SD 9.35; 0 to 45 mSv). Over the recommended ten years of surveillance the estimated total effective dose was 106 mSv. CONCLUSIONS: Surveillance of completely resected GEP NET results in cumulative radiation doses in the range associated with secondary malignancy development. Strategies to minimize radiation exposure in surveillance should be considered in future guideline development.

COMP Report: A survey of radiation safety regulations for medical imaging x-ray equipment in Canada.

X-ray regulations and room design methodology vary widely across Canada. The Canadian Organization of Medical Physicists (COMP) conducted a survey in 2016/2017 to provide a useful snapshot of existing variations in rules and methodologies for human patient medical imaging facilities. Some jurisdictions no longer have radiation safety regulatory requirements and COMP is concerned that lack of regulatory oversight might erode safe practices. Harmonized standards will facilitate oversight that will ensure continued attention is given to public safety and to control workplace exposure. COMP encourages all Canadian jurisdictions to adopt the dose limits and constraints outlined in Health Canada Safety Code 35 with the codicil that the design standards be updated to those outlined in NCRP 147 and BIR 2012.

Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model.

OBJECTIVES: Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG) metabolism and tumor blood flow mismatch would correlate with tumor hypoxia. METHODS: Liver perfusion computed tomography (CT) and 18F-FDG positron emission tomography (PET) imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2). Tumor blood flow (BF) and standardized uptake value (SUV) were measured to calculate flow-metabolism ratio (FMR). Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining. RESULTS: Weak correlations were found between blood volume (BV) and pO2 level (r = 0.425, P = 0.004), SUV and pO2 (r = -0.394, P = 0.007), FMR and pimonidazole staining score (r = -0.388, P = 0.031). However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001). CONCLUSIONS: FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.

Ultra-Low-Dose Sparse-View Quantitative CT Liver Perfusion Imaging.

Radiation dose of computed tomography liver perfusion imaging can be reduced by collecting fewer x-ray projections in each gantry rotation, but the resulting aliasing artifacts could affect the hepatic perfusion measurement. We investigated the effect of projection undersampling on the assessment of hepatic arterial blood flow (HABF) in hepatocellular carcinoma (HCC) when dynamic contrast-enhanced (DCE) liver images were reconstructed with filtered backprojection (FBP) and compressed sensing (CS). DCE liver images of a patient with HCC acquired with a 64-row CT scanner were reconstructed from all the measured projections (984-view) with the standard FBP and from one-third (328-view) and one-fourth (246-view) of all available projections with FBP and CS. Each of the 5 sets of DCE liver images was analyzed with a model-based deconvolution algorithm from which HABF maps were generated and compared. Mean HABF in the tumor and normal tissue measured by the 328-view CS and FBP protocols was within 5% differences from that assessed by the reference full-view FBP protocol. In addition, the tumor size measured by using the 328-view CS and FBP average images was identical to that determined by using the full-view FBP average image. By contrast, both the 246-view CS and FBP protocols exhibited larger differences (>20%) in anatomical and functional assessments compared with the full-view FBP protocol. The preliminary results suggested that computed tomography perfusion imaging in HCC could be performed with 3 times less projection measurement than the current full-view protocol (67% reduction in radiation dose) when either FBP or CS was used for image reconstruction.

Efficacy of Selective Brain Cooling Using a Nasopharyngeal Method in Piglets.

BACKGROUND: Mild hypothermia is an effective neuroprotective strategy for a variety of acute brain injuries. Cooling the nasopharynx may offer the capability to cool the brain selectively due to anatomic proximity of the internal carotid artery to the cavernous sinus. This study investigated the feasibility and efficiency of nasopharyngeal brain cooling by continuously blowing room temperature or cold air at different flow rates into the nostrils of normal newborn piglets. METHODS: Experiments were conducted on thirty piglets (n = 30, weight = 2.7 ± 1.5 kg). Piglets were anesthetized with 1­2% isoflurane and were randomized to receive one of four different nasopharyngeal cooling treatments: I. Room temperature at a flow rate of 3­4 L min(−1) (n = 6); II. −1 ± 2 °C at a flow rate of 3­4 L min(−1) (n = 6); III. Room temperature at a flow rate of 14­15 L min(−1) (n = 6); IV. −8 ± 2 °C at a flow rate of 14­15 L min(−1) (n = 6). To control for the normal thermal regulatory response of piglets without nasopharyngeal cooling, a control group of piglets (n = 6) had their brain temperature monitored without nasopharyngeal cooling. The duration of treatment was 60 min, with additional 30 min of observation. RESULTS: In group I, median cooling rate was 1.7 ± 0.9 °C/h by setting the flow rate of room temperature air to 3­4 L min(−1). Results of comparing different temperatures and flow rates in the nasopharyngeal cooling approach reveal that the brain temperature could be reduced rapidly at a rate of 5.5 ± 1.1 °C/h by blowing −8 ± 2 °C air at a flow rate of 14­15 L min(−1). CONCLUSIONS: Nasopharyngeal cooling via cooled insufflated air can lower the brain temperature, with higher flows and lower temperatures of insufflated air being more effective.

Perfusion CT estimates photosensitizer uptake and biodistribution in a rabbit orthotopic pancreatic cancer model: a pilot study.

RATIONALE AND OBJECTIVES: It was hypothesized that perfusion computed tomography (CT), blood flow (BF), blood volume (BV), and vascular permeability surface area (PS) product parameters would be predictive of therapeutic anticancer agent uptake in pancreatic cancer, facilitating image-guided interpretation of human treatments. The hypothesis was tested in an orthotopic rabbit model of pancreatic cancer, by establishing the model, imaging with endoscopic ultrasound (EUS) and contrast CT, and spatially comparing the perfusion maps to the ex vivo uptake values of the injected photosensitizer, verteporfin. MATERIALS AND METHODS: Nine New Zealand white rabbits underwent direct pancreas implantation of VX2 tumors, and CT perfusion or EUS was performed 10 days postimplantation. Verteporfin was injected during CT imaging, and the tissue was removed 1 hour postinjection for frozen tissue fluorescence scanning. Region-of-interest comparisons of CT data with ex vivo fluorescence and histopathologic staining were performed. RESULTS: Dynamic contrast-enhanced CT showed enhanced BF, BV, and PS in the tumor rim and decreased BF, BV, and PS in the tumor core. Significant correlations were found between ex vivo verteporfin concentration and each of BF, BV, and PS. CONCLUSIONS: The efficacy of verteporfin delivery in tumors is estimated by perfusion CT, providing a noninvasive method of mapping photosensitizer dose.

Brain Cooling With Ventilation of Cold Air Over Respiratory Tract in Newborn Piglets: An Experimental and Numerical Study.

We investigate thermal effects of pulmonary cooling which was induced by cold air through an endotracheal tube via a ventilator on newborn piglets. A mathematical model was initially employed to compare the thermal impact of two different gas mixtures, O2-medical air (1:2) and O2-Xe (1:2), across the respiratory tract and within the brain. Following mathematical simulations, we examined the theoretical predictions with O2-medical air condition on nine anesthetized piglets which were randomized to two treatment groups: 1) control group ([Formula: see text]) and 2) pulmonary cooling group ([Formula: see text]). Numerical and experimental results using O2-medical air mixture show that brain temperature fell from 38.5 °C and 38.3 °C ± 0.3 °C to 35.7 °C ± 0.9 °C and 36.5 °C ± 0.6 °C during 3 h cooling which corresponded to a mean cooling rate of 0.9 °C/h ± 0.2 °C/h and 0.6 °C/h ± 0.1 °C/h, respectively. According to the numerical results, decreasing the metabolic rate and increasing air velocity are helpful to maximize the cooling effect. We demonstrated that pulmonary cooling by cooling of inhalation gases immediately before they enter the trachea can slowly reduce brain and core body temperature of newborn piglets. Numerical simulations show no significant differences between two different inhaled conditions, i.e., O2-medical air (1:2) and O2-Xe (1:2) with respect to cooling rate.

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors.

PURPOSE: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. METHODS: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. RESULTS: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. CONCLUSIONS: Based on the authors' animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.

Effect of an angiogenesis inhibitor on hepatic tumor perfusion and the implications for adjuvant cytotoxic therapy.

PURPOSE: To determine whether dynamic contrast material-enhanced (DCE) computed tomography (CT) can help identify hepatic tumor perfusion response to vascular remodeling induced by antiangiogenesis treatment in a rabbit model. MATERIALS AND METHODS: The study was approved by the Animal Use Subcommittee of the University Council on Animal Care. DCE CT hepatic perfusion measurements were performed in the livers of 20 rabbits implanted with VX2 carcinoma. Vascular remodeling was induced with thalidomide dissolved in dimethyl sulfoxide and sterile water, starting at a tumor diameter of 0.7 cm±0.1 and continuing until metastatic lung nodules were observed. The control group (n=8) was given an equivalent volume of the vehicle. The therapy group was subdivided into animals that survived for more than 24 days without lung metastasis (responder group, n=5) or those that survived for less than 24 days (nonresponder group, n=7). Data were analyzed with the Kruskal-Wallis or Friedman rank test and reported as medians and interquartile ranges. RESULTS: DCE CT depicted differential perfusion change within the therapy group after treatment. By day 4, hepatic blood volume (HBV) in the responder group decreased by 29.2% (-32.5% to -11.8%) relative to that before treatment and was significantly different from that in the nonresponder (P=.048) and control (P=.011) groups, where HBV remained stable. By day 8, hepatic artery blood flow decreased by 50.0% (-59.08% to -21.05%) relative to that before treatment in the responder group and was significantly different from that in the nonresponder and control groups (P=.030 for both), which remained stable at -3.5% (-8.5% to 28.7%, P=.50) and -10.0% (-33.8% to 10.4%, P=.48), respectively. CONCLUSION: DCE CT can help differentiate responders from nonresponders by their early differential perfusion response to antiangiogenesis therapy.

Hepatic perfusion in a tumor model using DCE-CT: an accuracy and precision study.

In the current study we investigate the accuracy and precision of hepatic perfusion measurements based on the Johnson and Wilson model with the adiabatic approximation. VX2 carcinoma cells were implanted into the livers of New Zealand white rabbits. Simultaneous dynamic contrast-enhanced computed tomography (DCE-CT) and radiolabeled microsphere studies were performed under steady-state normo-, hyper- and hypo-capnia. The hepatic arterial blood flows (H(A)BF) obtained using both techniques were compared with ANOVA. The precision was assessed by the coefficient of variation (CV). Under normo-capnia the microsphere H(A)BF were 51.9 +/- 4.2, 40.7 +/- 4.9 and 99.7 +/- 6.0 ml min(-1) (100 g)(-1) while DCE-CT H(A)BF were 50.0 +/- 5.7, 37.1 +/- 4.5 and 99.8 +/- 6.8 ml min(-1) (100 g)(-1) in normal tissue, tumor core and rim, respectively. There were no significant differences between H(A)BF measurements obtained with both techniques (P > 0.05). Furthermore, a strong correlation was observed between H(A)BF values from both techniques: slope of 0.92 +/- 0.05, intercept of 4.62 +/- 2.69 ml min(-1) (100 g)(-1) and R(2) = 0.81 +/- 0.05 (P < 0.05). The Bland-Altman plot comparing DCE-CT and microsphere H(A)BF measurements gives a mean difference of -0.13 ml min(-1) (100 g)(-1), which is not significantly different from zero. DCE-CT H(A)BF is precise, with CV of 5.7, 24.9 and 1.4% in the normal tissue, tumor core and rim, respectively. Non-invasive measurement of H(A)BF with DCE-CT is accurate and precise. DCE-CT can be an important extension of CT to assess hepatic function besides morphology in liver diseases.

Correlation between hepatic tumor blood flow and glucose utilization in a rabbit liver tumor model.

PURPOSE: To prospectively determine the relationship between hepatic tumor blood flow and glucose utilization in vivo by using a combined positron emission tomographic (PET)/computed tomographic (CT) scanner. MATERIALS AND METHODS: The animal care and use subcommittee at the University of Western Ontario approved this study. VX2 carcinoma cells were implanted in the livers of eight male New Zealand white rabbits. Functional CT was performed before tumor implantation and every 4 days thereafter. Each examination consisted of two phases: In the first phase, 30-second cine breath-hold scanning was performed with simultaneous injection of 5 mL of contrast material. In the second phase, 4-second cine scanning was performed without breath holding every 10 seconds for 2 minutes. Second-phase CT images were coregistered with first-phase images to eliminate breathing artifacts. The weighted summation of the aortic and portal venous time-attenuation curves was deconvolved against curves from the liver to derive hepatic blood flow (HBF). Five animals underwent fluorine 18 fluorodeoxyglucose (FDG) scanning before and every 8 days after implantation. FDG uptake was measured as standardized uptake value (SUV). Data were analyzed with repeated-measures analysis of variance and the Tukey-Kramer multiple comparison test. Linear regression was used to compare SUV and HBF in tumors and normal tissue. RESULTS: In the hypovascular tumor core, (a) mean HBF decreased from 262 mL.min-1.100 g-1+/-22 (standard deviation) at baseline to 101 mL.min-1.100 g-1+/-62 at the end of the study (P<.05) and (b) mean SUV increased from 2.12 g/mL+/-0.06 to 4.56 g/mL+/-0.73 (P<.05) during the same period. CONCLUSION: Functional CT in combination with FDG PET can be used to observe changes in HBF and glucose utilization in a growing liver tumor.