Assessing the Accuracy of a Deep Learning Method to Risk Stratify Indeterminate Pulmonary Nodules.

Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep learning method to improve the management of IPNs.Methods: A Lung Cancer Prediction Convolutional Neural Network model was trained using computed tomography images of IPNs from the National Lung Screening Trial, internally validated, and externally tested on cohorts from two academic institutions.Measurements and Main Results: The areas under the receiver operating characteristic curve in the external validation cohorts were 83.5% (95% confidence interval [CI], 75.4-90.7%) and 91.9% (95% CI, 88.7-94.7%), compared with 78.1% (95% CI, 68.7-86.4%) and 81.9 (95% CI, 76.1-87.1%), respectively, for a commonly used clinical risk model for incidental nodules. Using 5% and 65% malignancy thresholds defining low- and high-risk categories, the overall net reclassifications in the validation cohorts for cancers and benign nodules compared with the Mayo model were 0.34 (Vanderbilt) and 0.30 (Oxford) as a rule-in test, and 0.33 (Vanderbilt) and 0.58 (Oxford) as a rule-out test. Compared with traditional risk prediction models, the Lung Cancer Prediction Convolutional Neural Network was associated with improved accuracy in predicting the likelihood of disease at each threshold of management and in our external validation cohorts.Conclusions: This study demonstrates that this deep learning algorithm can correctly reclassify IPNs into low- or high-risk categories in more than a third of cancers and benign nodules when compared with conventional risk models, potentially reducing the number of unnecessary invasive procedures and delays in diagnosis.

Detrimental effects of nitroglycerin use during regadenoson vasodilator stress testing: A cautionary tale.

Vasodilator agents such as adenosine and regadenoson are commonly used pharmacologic stressors to assess for ischemia in patients undergoing myocardial perfusion studies. The recommended reversal agent for this mode of stress is aminophylline, although nitroglycerin is commonly administered as an attempt to reverse the symptoms or electrocardiographic (EKG) changes during the stress test. We demonstrate through two cases that incorrect administration of nitroglycerin can induce hypotension and worsen coronary steal, whereas appropriate administration of aminophylline can reverse the effects of pharmacologic vasodilators. While nitroglycerin is often used in patients with organic angina, it has the potential to worsen ischemia in the setting of pharmacologic vasodilator administration. These cases underscore the importance of administering the correct reversal agent for pharmacologic stress tests.

Spectral analysis of non-contrast fluoroscopy for evaluation of pulmonary perfusion: Feasibility and sensitivity testing with a phantom.

BACKGROUND: Oscillating x-ray attenuation in the lungs provides an opportunity to evaluate pulmonary perfusion without contrast. Recent intensity-based methods have been compared to pulmonary scintigraphy and CT angiography but lack rigorous phantom studies. PURPOSE: A new method to quantify the periodic signal amplitude was employed using spectral analysis. Performance was characterized using a water phantom capable of creating an oscillating x-ray attenuation at physiologic amplitudes. Feasibility in detecting abnormal perfusion was performed on a volunteer with pulmonary vascular disease and compared to pulmonary angiography, the clinical gold standard. METHODS: For each fluoroscopic acquisition, the normalized temporal signal from each pixel was decomposed into its frequency components using Fourier transformation, and the spectral amplitude, defined as the x-ray pulsatility index (XPI), was determined at the desired frequency using a band-pass filter. XPI was displayed as a pixel-wise parametric colormap. Based on XPI maps generated using two human volunteers, a water bath phantom was constructed with a fluctuating fluid height and a 1 cm diameter pulsatility defect. Contrast-to-noise (CNR) of the defect was measured using fluoroscopy images acquired at variable fluid height fluctuation (0.1-1.9 mm) and oscillation frequency (30-60 bpm). Various sampling frame rates (3-30 fps) and acquisition durations (1.8-8 s) using truncated datasets were reconstructed from full datasets. Fluoroscopic images were obtained in a patient just prior to pulmonary angiography in the same projection. RESULTS: XPI maps in human subjects showed high signal to background contrast with high central XPI measuring up to 0.5. Phantom experiments revealed CNR was linearly correlated to fluid height change (r2  = 0.998). CNR is proportional to increasing sampling frame rate and increasing acquisition duration as expected with Fourier analysis. XPI map displayed multifocal perfusion defects in good agreement with pulmonary angiography. CONCLUSION: Spectral analysis is an accurate and sensitive method to detect small changes in periodic x-ray attenuation using a short fluoroscopic acquisition. This method demonstrated good agreement to pulmonary angiography and shows promise for clinical imaging of pulmonary perfusion using standard fluoroscopic methods.

Radioimmunodetection of amyloid deposits in patients with AL amyloidosis.

Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.

First-in-Human PET Imaging and Estimated Radiation Dosimetry of l-[5-11C]-Glutamine in Patients with Metastatic Colorectal Cancer.

Altered metabolism is a hallmark of cancer. In addition to glucose, glutamine is an important nutrient for cellular growth and proliferation. Noninvasive imaging via PET may help facilitate precision treatment of cancer through patient selection and monitoring of treatment response. l-[5-11C]-glutamine (11C-glutamine) is a PET tracer designed to study glutamine uptake and metabolism. The aim of this first-in-human study was to evaluate the radiologic safety and biodistribution of 11C-glutamine for oncologic PET imaging. Methods: Nine patients with confirmed metastatic colorectal cancer underwent PET/CT imaging. Patients received 337.97 ± 44.08 MBq of 11C-glutamine. Dynamic PET acquisitions that were centered over the abdomen or thorax were initiated simultaneously with intravenous tracer administration. After the dynamic acquisition, a whole-body PET/CT scan was acquired. Volume-of-interest analyses were performed to obtain estimates of organ-based absorbed doses of radiation. Results:11C-glutamine was well tolerated in all patients, with no observed safety concerns. The organs with the highest radiation exposure included the bladder, pancreas, and liver. The estimated effective dose was 4.46E-03 ± 7.67E-04 mSv/MBq. Accumulation of 11C-glutamine was elevated and visualized in lung, brain, bone, and liver metastases, suggesting utility for cancer imaging. Conclusion: PET using 11C-glutamine appears safe for human use and allows noninvasive visualization of metastatic colon cancer lesions in multiple organs. Further studies are needed to elucidate its potential for other cancers and for monitoring response to treatment.

Preoperative coronary artery calcifications in veterans predict higher all-cause mortality in early-stage lung cancer: a cohort study.

BACKGROUND: Lung cancer patients often have comorbidities that may impact survival. This observational cohort study examines whether coronary artery calcifications (CAC) impact all-cause mortality in patients with resected stage I non-small cell lung cancer (NSCLC). METHODS: Veterans with stage I NSCLC who underwent resection at a single institution between 2005 and 2018 were selected from a prospectively collected database. Radiologists blinded to patient outcomes graded CAC severity (mild, moderate, or severe) in preoperative CT scans using a visual estimation scoring system. Inter-rater reliability was calculated using the kappa statistic. All-cause mortality was the primary outcome. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to compare time-to-death by varying CAC. RESULTS: The Veteran patients (n=195) were predominantly older (median age of 67) male (98%) smokers (96%). The majority (68%) were pathologic stage IA. Overall, 12% of patients had no CAC, 27% mild, 26% moderate, and 36% severe CAC. Median unadjusted survival was 8.8 years for patients with absent or mild CAC versus 6.3 years for moderate and 5.9 years for severe CAC (P=0.01). The adjusted hazard ratio for moderate CAC was 1.44 (95% CI, 0.85-2.46) and for severe CAC was 1.73 (95% CI, 1.03-2.88; P for trend <0.05). CONCLUSIONS: The presence of severe CAC on preoperative imaging significantly impacted the all-cause survival of patients undergoing resection for stage I NSCLC. This impact on mortality should be taken into consideration by multidisciplinary teams when making treatment plans for patients with early-stage disease.

Establishing a Cohort and a Biorepository to Identify Biomarkers for Early Detection of Lung Cancer: The Nashville Lung Cancer Screening Trial Cohort.

Rationale: A prospective longitudinal cohort of individuals at high risk of developing lung cancer was established to build a biorepository of carefully annotated biological specimens and low-dose computed tomography (LDCT) chest images for derivation and validation of candidate biomarkers for early detection of lung cancer.Objectives: The goal of this study is to characterize individuals with high risk for lung cancer, accumulating valuable biospecimens and LDCT chest scans longitudinally over 5 years.Methods: Participants 55-80 years of age with a 5-year estimated risk of developing lung cancer >1.5% were recruited and enrolled from clinics at the Vanderbilt University Medical Center, Veteran Affairs Medical Center, and Meharry Medical Center. Individual demographic characteristics were assessed via questionnaire at baseline. Participants underwent an LDCT scan, spirometry, sputum cytology, and research bronchoscopy at the time of enrollment. Participants will be followed yearly for 5 years. Positive LDCT scans are followed-up according to standard of care. The clinical, imaging, and biospecimen data are collected prospectively and stored in a biorepository. Participants are offered smoking cessation counseling at each study visit.Results: A total of 480 participants were enrolled at study baseline and consented to sharing their data and biospecimens for research. Participants are followed with yearly clinic visits to collect imaging data and biospecimens. To date, a total of 19 cancers (13 adenocarcinomas, four squamous cell carcinomas, one large cell neuroendocrine, and one small-cell lung cancer) have been identified.Conclusions: We established a unique prospective cohort of individuals at high risk for lung cancer, enrolled at three institutions, for whom full clinical data, well-annotated LDCT scans, and biospecimens are being collected longitudinally. This repository will allow for the derivation and independent validation of clinical, imaging, and molecular biomarkers of risk for diagnosis of lung cancer.Clinical trial registered with ClinicalTrials.gov (NCT01475500).

A dynamic model of CT scans for quantifying doubling time of ground glass opacities using histogram analysis.

We quantify a recent five-category CT histogram based classification of ground glass opacities using a dynamic mathematical model for the spatial-temporal evolution of malignant nodules. Our mathematical model takes the form of a spatially structured partial differential equation with a logistic crowding term. We present the results of extensive simulations and validate our model using patient data obtained from clinical CT images from patients with benign and malignant lesions.

A weight index for the standardized uptake value in 2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography.

INTRODUCTION: Known errors in the standardized uptake value (SUV) caused by variations in subject weights W encountered can be corrected by lean body mass or body surface area (bsa) algorithms replacing W in calculations. However this is infrequently done. The aims of the work here are: quantify sensitivity to W, encourage SUV correction with an approach minimally differing from tradition, and show what improvements in the SUV coefficient of variation (cv) for a population can be expected. METHODS: Selected for analyses were 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed tomography (CT) scans at the University of Tennessee as well as from the literature. A weight sensitivity index was defined as -n=slope of ln(SUV/W) vs. lnW. The portion of the SUV variability due to this trend is removed by using the defined [formula: see text], or a virtually equal SUVm using [formula: see text], with Q and ID being tissue specific-activity and injected dose. [formula: see text] measures performance. Adapting to animal studies' tradition, [formula: see text] is preferred over the conventional [formula: see text]. RESULTS: For FDG in adults [formula: see text] from averaging over most tissues. In children, however, [formula: see text]. Tissues have the same index if their influx constants are independent of W. Suggested, therefore, is a very simplified [formula: see text], which is dimensionless and keeps the same population averages as traditional SUVs. It achieves [formula: see text]. Hence, for cv's of SUVs below approximately 1/3 improvements over tradition are possible, leading to F's<0.95. Accounting additionally for height, as in SUVbsa, gives very little improvement over the simplified approach here and gives essentially the same F's as SUVm. CONCLUSIONS: Introduced here is a weight index useful in reducing variability and further understanding the SUV. Addressing weight sensitivity is appropriate where the cv of the SUVs is below about 1/3. Proposed is the very simple approach of using an average of an adult patient's weight and approximately 70 kg for FDG SUV calculations. Unlike other approaches the dimensionless population average of SUVms is unchanged from tradition.

Radiological Image Traits Predictive of Cancer Status in Pulmonary Nodules.

Purpose: We propose a systematic methodology to quantify incidentally identified pulmonary nodules based on observed radiological traits (semantics) quantified on a point scale and a machine-learning method using these data to predict cancer status.Experimental Design: We investigated 172 patients who had low-dose CT images, with 102 and 70 patients grouped into training and validation cohorts, respectively. On the images, 24 radiological traits were systematically scored and a linear classifier was built to relate the traits to malignant status. The model was formed both with and without size descriptors to remove bias due to nodule size. The multivariate pairs formed on the training set were tested on an independent validation data set to evaluate their performance.Results: The best 4-feature set that included a size measurement (set 1), was short axis, contour, concavity, and texture, which had an area under the receiver operator characteristic curve (AUROC) of 0.88 (accuracy = 81%, sensitivity = 76.2%, specificity = 91.7%). If size measures were excluded, the four best features (set 2) were location, fissure attachment, lobulation, and spiculation, which had an AUROC of 0.83 (accuracy = 73.2%, sensitivity = 73.8%, specificity = 81.7%) in predicting malignancy in primary nodules. The validation test AUROC was 0.8 (accuracy = 74.3%, sensitivity = 66.7%, specificity = 75.6%) and 0.74 (accuracy = 71.4%, sensitivity = 61.9%, specificity = 75.5%) for sets 1 and 2, respectively.Conclusions: Radiological image traits are useful in predicting malignancy in lung nodules. These semantic traits can be used in combination with size-based measures to enhance prediction accuracy and reduce false-positives. Clin Cancer Res; 23(6); 1442-9. ©2016 AACR.

Safety and Efficacy of 68Ga-DOTATATE PET/CT for Diagnosis, Staging, and Treatment Management of Neuroendocrine Tumors.

UNLABELLED: Our purpose was to evaluate the safety and efficacy of (68)Ga-DOTATATE PET/CT compared with (111)In-pentetreotide imaging for diagnosis, staging, and restaging of pulmonary and gastroenteropancreatic neuroendocrine tumors. METHODS: (68)Ga-DOTATATE PET/CT and (111)In-pentetreotide scans were obtained for 78 of 97 consecutively enrolled patients with known or suspected pulmonary or gastroenteropancreatic neuroendocrine tumors. Safety and toxicity were measured by comparing vital signs, serum chemistry values, or acquisition-related medical complications before and after (68)Ga-DOTATATE injection. Added value was determined by changes in treatment plan when (68)Ga-DOTATATE PET/CT results were added to all prior imaging, including (111)In-pentetreotide. Interobserver reproducibility of (68)Ga-DOTATATE PET/CT scan interpretation was measured between blinded and nonblinded interpreters. RESULTS: (68)Ga-DOTATATE PET/CT and (111)In-pentetreotide scans were significantly different in impact on treatment (P < 0.001). (68)Ga-DOTATATE PET/CT combined with CT or liver MRI changed care in 28 of 78 (36%) patients. Interobserver agreement between blinded and nonblinded interpreters was high. No participant had a trial-related event requiring treatment. Mild, transient events were tachycardia in 1, alanine transaminase elevation in 1, and hyperglycemia in 2 participants. No clinically significant arrhythmias occurred. (68)Ga-DOTATATE PET/CT correctly identified 3 patients for peptide-receptor radiotherapy incorrectly classified by (111)In-pentetreotide. CONCLUSION: (68)Ga-DOTATATE PET/CT was equivalent or superior to (111)In-pentetreotide imaging in all 78 patients. No adverse events requiring treatment were observed. (68)Ga-DOTATATE PET/CT changed treatment in 36% of participants. Given the lack of significant toxicity, lower radiation exposure, and improved accuracy compared with (111)In-pentetreotide, (68)Ga-DOTATATE imaging should be used instead of (111)In-pentetreotide imaging where available.

2-deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography sensitivity to serum glucose: a survey and diagnostic applications.

OBJECTIVE: The positron emission tomography (PET) clinical utility of the sensitivity (gamma) of uptake (Q) to a change in plasma glucose concentration (C) is investigated. METHODS: Gamma is obtained from data as [ln(Q (2)/Q (1))] / [ln(C(2)/C(1))], using previously published intrapatient studies varying C within a single patient and some interpatient ones. It can be theoretically related to the half-saturation constant in the Michaelis-Menten quantification of competitive uptake. One of its uses is making uptake corrections for desired vs. actual C using Q(2) = Q(1) (C(2)/C(1))(gamma). RESULTS: Intrapatient studies proved to be preferable to interpatient ones, and a 2-deoxy-2-[F-18]fluoro-D-glucose (FDG)-PET survey with analyses for gamma yielded the following result: usually the gamma values of tumors and brain tissues were near -1, whereas those of other noncerebral tissues were near 0. Regarding correcting uptakes for C, instead of a universally assumed and applied gamma = -1, corrections should be for a single tissue using its known gamma. An advantageous use of gamma is predicting how C affects image contrast, including where glucose loading is sometimes preferable to fasting. CONCLUSIONS: A potentially useful quantifier of uptake sensitivity to plasma glucose has been defined and values obtained. Correcting uptakes to some standard C requires special care. gamma can help PET clinicians select fasting or loading to achieve glucose levels for optimum contrast.

Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval.

PURPOSE: To use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up. METHODS: We performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3-13 mm diameter in 71 patients who underwent 3-9 repeat vCT studies for clinical evaluation of pulmonary nodules. Calculated volume standard deviation as a function of mean nodule volume was used to compute error in estimated growth rate. This error was then used to determine the optimal patient follow-up scan interval while fixing the false positive rate at 5%. RESULTS: Linear regression of nodule volume standard deviation versus the mean nodule volume for stable non-calcified nodules yielded a slope of 0.057 ± 0.002 (r2 = 0.79, p<0.001). For calcified stable nodules, the regression slope was 0.052 ± 0.005 (r2 = 0.65, p = 0.03). Using this with the error propagation formula, the optimal patient follow-up scan interval was calculated to be 81 days, independent of initial nodule volume. CONCLUSIONS: Reproducibility of vCT is excellent, and the standard error is proportional to the mean calculated nodule volume for the range of nodules examined. This relationship constrains statistical certainty of vCT calculated doubling times and results in an optimal scan interval that is independent of the initial nodule volume.

Optimizing imaging time for improved performance in oncology PET studies.

PURPOSE: The potential for improving the diagnostic performance of static positron imaging tomography (PET) by judiciously choosing optimum post-injection imaging times is investigated. PROCEDURES: Dynamic and whole-body scan data, from 2-deoxy-2-[18F]fluoro-D-glucose (FDG) oncological studies, are analyzed for changing standardized uptake value (SUV) behavior with increasing post-injection times at either single- or multiple-bed positions. Model-based interpretations address d(SUV)/dt, shown to correlate with SUV, and the contrast ratio for a tumor and its surroundings. A method for correcting measurements to a standardized time is given. RESULTS: Both data and model-based equations suggest that starting data acquisition later than the average 55 +/- 15 (SD) minutes post-injection reported in the FDG literature can improve contrast ratios. Considerations for choosing an optimum time from a clinical standpoint are listed. CONCLUSIONS: It is concluded that the appropriate time for each particular protocol can be found with the aid of the information presented here. True optimization, however, remains a complex issue.

Characterization of uptake of 2-deoxy-2-[18F]fluoro-D-glucose by fungal-associated inflammation: the differential uptake ratio for blastomyces-associated lesions is as high as for lymphoma and higher than for turpentine abscesses in experimentally induced lesions in rats.

PURPOSE: The objective of this investigation was to determine the biologic basis and the significance of uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using experimentally created fungal lesions in rats. PROCEDURES: Uptake of FDG by experimentally induced Blastomyces granulomas was compared with uptake by turpentine abscesses (Group 1) and by lymphomas (Group 2) using the differential uptake ratio (DUR) measured one hour after administration of 2 mCi FDG intravenously. Frozen tissue sections of Blastomyces lesions and turpentine abscesses were placed in contact with radiographic film for macroautoradiography. RESULTS: In rats in Group 1, the median (range) DUR for the Blastomyces granulomas was 1.9 (1.1-2.6) and was significantly higher than the DUR for turpentine abscesses 0.9 (0.6-1.4) and muscle 0.2 (0.1-0.5; P < 0.001). In Group 2, the median (range) DUR for the Blastomyces granulomas, lymphomas, and muscle from the rats in Group 2 were 1.8 (1.2-3.4), 1.9 (1.0-4.0), and 0.2 (0.1-0.3), respectively. There was no significant difference between the DUR of Blastomyces granulomas and lymphomas. Macroautoradiographs of the Blastomyces granulomas revealed intense uptake of FDG in the region occupied by the yeast organisms and the granulomatous inflammation. CONCLUSIONS: Blastomyces granulomas typically have high uptake of FDG associated with the region composed of the granulomatous inflammatory reaction and Blastomyces yeast organisms.

Characterization of uptake of 2-deoxy-2-[18F] fluoro-D-glucose by fungal-associated inflammation: the standardized uptake value is greater for lesions of blastomycosis than for lymphoma in dogs with naturally occurring disease.

PURPOSE: Based on limited reports, fungal lesions can have remarkably high intensity uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) on positron emission tomography (PET) images. The purpose of this investigation was to compare the standardized uptake value (SUV) of naturally occurring lesions of blastomycosis with the SUV of naturally occurring lymphoma in a series of dogs. PROCEDURES: Five dogs with naturally occurring blastomycosis and three dogs with lymphoma underwent whole-body FDG-PET prior to receiving any treatment for their disease. RESULTS: The (mean +/- SD) SUV for 13 blastomycosis lesions was 7.7 +/- 2.0 versus a mean for 17 lymphomas of 4.8 +/- 1.8. These values were significantly different (P = 0.0537). There was overlap between the SUV of Blastomyces-associated lesions versus lymphomas, but a cut-off SUV of 7.0 was 100% specific for Blastomyces lesions. Numerous sites of disease were detected on the FDG-PET images that were not detected clinically. CONCLUSIONS: FDG-PET is useful for determining the extent of disease in dogs with blastomycosis. The SUV for Blastomyces-associated lesions are as high or higher than for malignant lymphoma. Due to the similarities in canine and human blastomycosis and lymphomas, similar results would be predicted in human patients. In regions where blastomycosis is endemic, Blastomyces granulomas should be considered a differential diagnosis for lesions with high intensity uptake of FDG.

Improved treatment planning for boron neutron capture therapy for glioblastoma multiforme using fluorine-18 labeled boronophenylalanine and positron emission tomography.

Boron neutron capture therapy (BNCT) is a cancer brachytherapy based upon the thermal neutron reaction: 10B(n,alpha)7Li. The efficacy of the treatment depends primarily upon two conditions being met: (a) the preferential concentration of a boronated compound in the neoplasm and (b) an adequate fluence of thermal neutrons delivered to the neoplasm. The boronated amino acid, para-boronophenylalanine (BPA), is the agent widely used in clinical trials to deliver 10B to the malignancy. Positron emission tomography (PET) can be used to generate in vivo boron distribution maps by labeling BPA with the positron emitting nuclide fluorine-18. The incorporation of the PET-derived boron distribution maps into current treatment planning protocols is shown to provide improved treatment plans. Using previously established protocols, six patients with glioblastoma had 18BPA PET scans. The PET distribution maps obtained were used in the conventional BNCT treatment codes. The isodose curves derived from the PET data are shown to differ both qualitatively and quantitatively from the conventional isodose curves that were derived from calculations based upon the assumption of uniform uptake of the pharmaceutical in tumor and normal brain regions. The clinical course of each of the patients who eventually received BNCT (five of the six patients) was compared using both sets of isodose calculations. The isodose contours based upon PET derived distribution data appear to be more consistent with the patients' clinical course.

Minimally invasive parathyroidectomy: how effective is preoperative sestamibi scanning?

Minimally invasive parathyroidectomy (MIP) guided by preoperative sestamibi scanning has been shown to reduce operative time, hospital stay, and cost in treating primary hyperparathyroidism. However, controversy exists over routine preoperative sestamibi scanning. The purpose of this study was to determine the utility of sestamibi scanning at our institution as part of the MIP protocol and to analyze calcium and parathyroid hormone levels as possible predictors of successful sestamibi scanning. Charts of 37 consecutive patients undergoing MIP at our institution were reviewed, and age, sex, preoperative calcium, and parathyroid (PTH) levels, invasiveness of procedure, and pathologic diagnosis were recorded. Sestamibi scans were reviewed and scored by 4 nuclear medicine faculty based on the level of suspicion for parathyroid adenoma. Neither calcium nor PTH correlated significantly with sestamibi scan score (Spearman coefficient, r = 0.075, P = 0.67 and r = 0.277, P = 0.10, respectively). Receiver-operating-characteristic (ROC) analysis showed sestamibi scanning to have sensitivity and specificity in predicting MIP completion (87% and 68%). Logistic regression showed only sestamibi scan (P = 0.038), not calcium or PTH (P = 0.977 and P = 0.767) to be predictive of MIP completion. In conclusion, sestamibi scanning effectively predicted the ability to perform MIP. However, preoperative calcium and PTH predicted neither sestamibi scan results nor completion of MIP.

Nuclear medicine practices in the 1950s through the mid-1970s and occupational radiation doses to technologists from diagnostic radioisotope procedures.

Data on occupational radiation exposure from nuclear medicine procedures for the time period of the 1950s through the 1970s is important for retrospective health risk studies of medical personnel who conducted those activities. However, limited information is available on occupational exposure received by physicians and technologists who performed nuclear medicine procedures during those years. To better understand and characterize historical radiation exposures to technologists, the authors collected information on nuclear medicine practices in the 1950s, 1960s, and 1970s. To collect historical data needed to reconstruct doses to technologists, a focus group interview was held with experts who began using radioisotopes in medicine in the 1950s and the 1960s. Typical protocols and descriptions of clinical practices of diagnostic radioisotope procedures were defined by the focus group and were used to estimate occupational doses received by personnel, per nuclear medicine procedure, conducted in the 1950s to 1960s using radiopharmaceuticals available at that time. The radionuclide activities in the organs of the reference patient were calculated using the biokinetic models described in ICRP Publication 53. Air kerma rates as a function of distance from a reference patient were calculated by Monte Carlo radiation transport calculations using a hybrid computational phantom. Estimates of occupational doses to nuclear medicine technologists per procedure were found to vary from less than 0.01 µSv (thyroid scan with 1.85 MBq of administered I-iodide) to 0.4 µSv (brain scan with 26 MBq of Hg-chlormerodin). Occupational doses for the same diagnostic procedures starting in the mid-1960s but using Tc were also estimated. The doses estimated in this study show that the introduction of Tc resulted in an increase in occupational doses per procedure.

Measured human dosimetry of 68Ga-DOTATATE.

UNLABELLED: Measured human dosimetry of the (68)Ga-labeled synthetic somatostatin analog (68)Ga-DOTATATE has not been reported in the peer-reviewed literature. (68)Ga-DOTATATE is an investigational PET/CT imaging agent that binds with high affinity to somatostatin receptor subtype 2, found on many human cancers, most classically neuroendocrine tumors but also others. Reporting of measured dosimetry of (68)Ga-DOTATATE could be useful for investigations for diagnosis, staging, and restaging of somatostatin receptor-expressing tumors. METHODS: We performed measured dosimetry with (68)Ga-DOTATATE PET/CT scanning in 6 volunteer human subjects as part of an Institutional Review Board-approved biodistribution investigation of the use of this radiopharmaceutical for possible future use in the diagnosis of indeterminate lung nodules or lung cancer. Five subjects were imaged at 3 time points, and 1 subject was imaged at 2 time points. Dosimetry was then measured for the whole body and for specific organs. RESULTS: There were no observed adverse events to the radiopharmaceutical in the immediate or delayed time frames, with a follow-up of 1 y. One patient had stage IV non-small cell lung cancer and remains alive but with disease progressing on treatment. For the other 5 patients, it was ultimately proven that they had benign nodules. The measured dosimetry shows that the critical organ with (68)Ga-DOTATATE is the spleen, followed by the uroepithelium of the bladder, the kidneys, and the liver, in that order. Organ-specific and whole-body dosimetries for (68)Ga-DOTATATE were similar to but often slightly greater than those for (68)Ga-DOTATOC or (68)Ga-DOTANOC but less than those for (111)In-diethylenetriaminepentaacetic acid-octreotide. CONCLUSION: No toxicity was observed in our 6 patients, and no adverse events occurred. The measured human dosimetry of (68)Ga-DOTATATE is similar to that of other (68)Ga-labeled somatostatin receptor analogs.