O’Connor, Michael K.

Abstract The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.

Abstract Background High mammographic breast density is the primary reason for missed cancers or delayed detection on mammography, and is associated with a higher rate of advanced and interval cancers which increase breast cancer mortality. Digital breast tomosynthesis (DBT) has been shown to reduce false positive findings relative to 2D mammography but does not eliminate the potential for tumor masking in dense breasts due to the similar x-ray attenuation characteristics of tumors and normal fibroglandular tissue. Molecular Breast Imaging (MBI) performed with a dedicated gamma camera to detect functional uptake of a radiotracer, Tc-99m sestamibi, has been shown to reveal breast cancers obscured by density on mammography. In single-institution studies, adding MBI to 2D mammography in women with dense breasts detected an additional 5 to10 invasive cancers per 1000 screened, with modest increases in recall rate (6 to 8%) at a lower cost-per-cancer detected than mammography alone. Despite this promising evidence, the lack of multicenter trial data has limited wider acceptance. Also, MBI has yet to be compared to DBT, which in some centers has replaced 2D mammography screening. We present interim results from a multicenter trial comparing cancer detection rate of DBT and MBI in screening of women with mammographically dense breasts. Methods In this ongoing, prospective, multicenter clinical trial, asymptomatic women aged 40-75 years with dense breasts on prior mammogram and no prior history of supplemental screening are invited to undergo two annual rounds of concurrent DBT and MBI. MBI is performed with injection of 300 MBq Tc-99m sestamibi with a dual-head semiconductor-based gamma camera. Screening tests are interpreted independently. Here, preliminary cancer detection rates (cancers per 1000 women screened), recall rates, and biopsy rates of DBT and MBI for initial screening are reported. Results In 537 women out of a planned 3000 who have completed the first round of screening, 7 cancers were detected: one by DBT only and 6 by MBI only, giving cancer detection rates of 1.9 for DBT vs. 11.2 for MBI and incremental cancer detection rate of 9.3 for MBI. The one DBT-only cancer was a node-negative 0.8 cm invasive lobular carcinoma. All 6 cancers detected by MBI were invasive; 5 of 6 were node negative (median size 1.0 cm; range 0.6 to 2.6 cm). Recall rate was 11% (60/537) for DBT alone; 16% (84/537) for MBI alone, and 21% (115/537) for the combination. Biopsy was prompted by DBT in 13 patients (PPV 8% [1/13]); by MBI in 23 patients (PPV 26% [6/23]); and by the combination of modalities in 33 (PPV 21% [7/33]). Conclusion These preliminary results demonstrate that MBI detects invasive breast cancers occult on DBT in dense breasts. Data from a second screening round will allow calculation of sensitivity and specificity, and determination of the impact of screening MBI in reducing advanced (> 2 cm) and interval cancers. Additional planned analyses will evaluate a denoising algorithm for further reduction in MBI radiation dose to match that of DBT. Citation Format: Rhodes D, Hunt K, Conners A, Zingula S, Whaley D, Ellis R, Gasal Spilde J, Mehta R, Polley M-Y, O'Connor M, Hruska C. Molecular breast imaging and tomosynthesis to eliminate the reservoir of undetected cancer in dense breasts: The Density MATTERS trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD4-05.

PURPOSE Background parenchymal uptake (BPU), which describes the level of radiotracer uptake in normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor. Our objective was to develop and validate a deep learning model using image convolution to automatically categorize BPU on MBI. METHODS MBI examinations obtained for clinical and research purposes from 2004 to 2015 were reviewed to classify the BPU pattern using a standardized five-category scale. Two expert radiologists provided interpretations that were used as the reference standard for modeling. The modeling consisted of training and validating a convolutional neural network to predict BPU. Model performance was summarized in data reserved to test the performance of the algorithm at the per-image and per-breast levels. RESULTS Training was performed on 24,639 images from 3,133 unique patients. The model performance on the withheld testing data (6,172 images; 786 patients) was evaluated. Using direct matching on the predicted classification resulted in an accuracy of 69.4% (95% CI, 67.4% to 71.3%), and if prediction within one category was considered, accuracy increased to 96.0% (95% CI, 95.2% to 96.7%). When considering the breast-level prediction of BPU, the accuracy remained strong, with 70.3% (95% CI, 68.0% to 72.6%) and 96.2% (95% CI, 95.3% to 97.2%) for the direct match and allowance for one category, respectively. CONCLUSION BPU provided a robust target for training a convolutional neural network. A validated computer algorithm will allow for objective, reproducible encoding of BPU to foster its integration into risk-stratification algorithms.

AbstractBackgroundThe reproducibility of gastric emptying (GE) measured with scintigraphy in patients is poorly understood. Our aims were to assess the intra and inter‐individual reproducibility of these parameters in patients with upper gastrointestinal symptoms.MethodsSixty patients (21 diabetics, 39 non‐diabetics) with upper gastrointestinal symptoms underwent scintigraphic‐assessment of GE of a solid meal (296 kcal, 30% fat) over 4 hours on two occasions at an average interval of 15 days. The concordance correlation coefficient (CCC), intra and inter‐individual coefficients of variation (COV) of GE endpoints were analyzed.ResultsThe GE t1/2 was 134 ± 8 minutes (mean ± SEM) for the first and 128 ± 6 minutes for the second study. The mean (95% CI) CCC between the two studies was 0.79 (0.67, 0.87) for GE at 1 hour, 0.83 (0.75, 0.9) for GE at 2 hours, 0.54 (0.34, 0.7) for GE at 4 hours, and 0.79 (0.68, 0.86) for GE t1/2. However, in 18 of 60 patients (30%), the characterization of GE as normal, delayed, or rapid differed between the first and second studies. For gastric empting t1/2, the inter‐individual coefficients of variation was 40%; the intra‐individual COV was 20%, comparable in diabetics and non‐diabetics, and greater in patients with rapid (28%) than delayed (18%) or normal GE (12%).Conclusions & InferencesAmong patients with upper gastrointestinal symptoms, GE measured with scintigraphy is relatively reproducible. In 30% of cases, the interpretation was different between the two assessments. Hence, a diagnosis of gastroparesis based on a single study may occasionally be inaccurate.

ABSTRACT BACKGROUND AND PURPOSE SISCOM and STATISCOM were clinically proved to be effective for ictal/inter‐ictal single‐photon emission computed tomography (SPECT) analysis coregistered with magnetic resonance imaging (MRI) for seizure localization. Recently, a software package also became available for this analysis. This study aimed to investigate and compare the performance of these analysis methods for seizure localization. METHODS A total of 378 patients who underwent 99m Tc‐ethyl cysteinate dimer (ECD) SPECT scans were retrospectively reviewed and 28 remained after applying exclusion criteria. Their SPECT and MRI images were analyzed with SISCOM (with z ‐score of 1.5 and 2), STATISCOM, and MIMneuro, resulting in a total of 112 image data sets. Two experienced radiologists participated in the blind review process using a custom tool and they can mark up to two hyper‐ and/or hypoperfusion regions. Their review results were analyzed using the Jackknife Free Response Receiver‐Operating Characteristics (JAFROC) test and the JAFROC figure‐of‐merit (FoM) was reported for each method. The interobserver agreement was also assessed using Cohen's kappa test. RESULTS Based on the readers’ two choices, averaged FoM was 85.7%, 83.9%, 66.1%, and 51.8% for STATISCOM, MIMneuro, SISCOM ( z ‐score = 2), and SISCOM ( z ‐score = 1.5), respectively. The average confidence rating was 2.5, 2.3, 1.6, and 1.1 for STATISCOM, MIMneuro, SISCOM ( z ‐score = 2), and SISCOM ( z ‐score = 1.5), respectively. For interobserver agreement, kappa was .742 for STATISCOM, .816 for MIMneuro, .517 for SISCOM ( z ‐score = 2), and .441 for SISCOM ( z ‐score = 1.5; all P < .001). CONCLUSION Our study demonstrated that STATISCOM showed the best performance for seizure localization, which was closely followed by MIMneuro. In addition, MIMneuro was not inferior to SISCOM with either z ‐score.

Postprandial symptoms of bloating, distension, early satiety, and nausea are associated with impaired postprandial gastric accommodation, which is detectable by means of an intragastric, barostatically controlled balloon in the proximal stomach and by ultrasound in the distal stomach. Our aim was to develop a noninvasive method to measure the entire gastric accommodation reflex. In 10 healthy volunteers, we used single photon emission computed tomography (SPECT) to measure fasting and postprandial gastric volumes. This method involved intravenous injection of99mTc pertechnetate and gastric reconstruction of tomographic images with Analyze software. SPECT-Analyze imaging detects the postprandial gastric accommodation reflex in vivo. Mean fasting gastric volume was 182 ± 11 (SE) ml and mean postprandial volume was 690 ± 32 ml ( P < 0.001). Both proximal and distal segments of stomach showed a two- to almost fourfold difference in volumes postprandially. Intraobserver coefficients of variation in estimated fasting and postprandial volumes were 9 and 8%; interobserver variations were 13 and 12%, respectively. SPECT-Analyze noninvasively measures postprandial gastric (total, proximal, and distal) accommodation in humans. This method appears promising to compare the accommodation response in health and disease and to perform mechanistic studies of the accommodation response.

Central processing of visceral information in humans is incompletely understood. We aimed to demonstrate the feasibility of single photon emission computed tomography (SPECT) and to quantitate the changes in regional cerebral blood flow during rectal distension. Ten healthy volunteers underwent randomized sham and active rectal distensions on separate days, during which cerebral blood flow was assessed by intravenous technetium-99m ethyl cysteinate dimer (99mTc-ECD) SPECT. Three-dimensional coregistration of brain images was used to quantitate activation in four preselected cerebral foci and two control regions. Paired analysis compared blood flow during sham and active distensions. There was increased right anterior cingulate gyrus activity (6.5 ± 2.9%, P = 0.03) with active rectal distension. A 5.4 ± 2.4% reduction in blood flow in the superior parieto-occipital control region ( P = 0.04) suggested blood “redistribution” during stimulation. Marked variability in activation of the frontal cortex, thalamus/basal ganglia complex, and mesiotemporal lobe was noted. Thus rectal distension increases activity in the right anterior cingulate gyrus on average; other foci of cerebral activation are quite variable, suggesting a lack of specific cerebral projections during rectal stimulation.

PurposeThe purpose of this study was to perform a pilot evaluation of an integrated molecular breast imaging/ultrasound (MBI/US) system designed to enable, in real‐time, the registration of US to MBI and diagnostic evaluation of breast lesions detected on MBI.MethodsThe MBI/US system was constructed by modifying an existing dual‐head cadmium zinc telluride (CZT)‐based MBI gamma camera. The upper MBI detector head was replaced with a mesh panel, which allowed an ultrasound probe to access the breast. An optical tracking system was used to monitor the location of the ultrasound transducer, referenced to the MBI detector. The lesion depth at which ultrasound was targeted was estimated from analysis of previously acquired dual‐head MBI datasets. A software tool was developed to project the US field of view onto the current MBI image. Correlation of lesion location between both modalities with real‐time MBI/US scanning was confirmed in a breast phantom model and assessed in 12 patients with a breast lesion detected on MBI.ResultsCombined MBI/US scanning allowed for registration of lesions detected on US and MBI as validated in phantom experiments. In patient studies, successful registration was achieved in 8 of 12 (67%) patients, with complete registration achieved in seven and partial registration achieved in one patient. In 4 of 12 (37%) patients, lesion registration was not achieved, partially attributed to uncertainty in lesion depth estimates from MBI.ConclusionThe MBI/US system enabled successful registration of US to MBI in over half of patients studied in this pilot evaluation. Future studies are needed to determine if real‐time, registered US imaging of MBI‐detected lesions may obviate the need to proceed to more expensive procedures such as contrast‐enhanced breast MRI for diagnostic workup or biopsy of MBI findings.

Transplantation of gene-corrected autologous hepatocytes can cure metabolic disease in a preclinical pig model of hereditary tyrosinemia type 1.