Feasibility of free-breathing 19 F MRI image acquisition to characterize ventilation defects in CF and healthy volunteers at wash-in.

PURPOSE: To explore the feasibility of measuring ventilation defect percentage (VDP) using 19 F MRI during free-breathing wash-in of fluorinated gas mixture with postacquisition denoising and to compare these results with those obtained through traditional Cartesian breath-hold acquisitions. METHODS: Eight adults with cystic fibrosis and 5 healthy volunteers completed a single MR session on a Siemens 3T Prisma. 1 H Ultrashort-TE MRI sequences were used for registration and masking, and ventilation images with 19 F MRI were obtained while the subjects breathed a normoxic mixture of 79% perfluoropropane and 21% oxygen (O2 ). 19 F MRI was performed during breath holds and while free breathing with one overlapping spiral scan at breath hold for VDP value comparison. The 19 F spiral data were denoised using a low-rank matrix recovery approach. RESULTS: VDP measured using 19 F VIBE and 19 F spiral images were highly correlated (r = 0.84) at 10 wash-in breaths. Second-breath VDPs were also highly correlated (r = 0.88). Denoising greatly increased SNR (pre-denoising spiral SNR, 2.46 ± 0.21; post-denoising spiral SNR, 33.91 ± 6.12; and breath-hold SNR, 17.52 ± 2.08). CONCLUSION: Free-breathing 19 F lung MRI VDP analysis was feasible and highly correlated with breath-hold measurements. Free-breathing methods are expected to increase patient comfort and extend ventilation MRI use to patients who are unable to perform breath holds, including younger subjects and those with more severe lung disease.

Machine learning for automated and real-time two-dimensional to three-dimensional registration of the spine using a single radiograph.

OBJECTIVE: The goal of this work was to methodically evaluate, optimize, and validate a self-supervised machine learning algorithm capable of real-time automatic registration and fluoroscopic localization of the spine using a single radiograph or fluoroscopic frame. METHODS: The authors propose a two-dimensional to three-dimensional (2D-3D) registration algorithm that maximizes an image similarity metric between radiographic images to identify the position of a C-arm relative to a 3D volume. This work utilizes digitally reconstructed radiographs (DRRs), which are synthetic radiographic images generated by simulating the x-ray projections as they would pass through a CT volume. To evaluate the algorithm, the authors used cone-beam CT data for 127 patients obtained from an open-source de-identified registry of cervical, thoracic, and lumbar scans. They systematically evaluated and tuned the algorithm, then quantified the convergence rate of the model by simulating C-arm registrations with 80 randomly simulated DRRs for each CT volume. The endpoints of this study were time to convergence, accuracy of convergence for each of the C-arm's degrees of freedom, and overall registration accuracy based on a voxel-by-voxel measurement. RESULTS: A total of 10,160 unique radiographic images were simulated from 127 CT scans. The algorithm successfully converged to the correct solution 82% of the time with an average of 1.96 seconds of computation. The radiographic images for which the algorithm converged to the solution demonstrated 99.9% registration accuracy despite utilizing only single-precision computation for speed. The algorithm was found to be optimized for convergence when the search space was limited to a ± 45° offset in the right anterior oblique/left anterior oblique, cranial/caudal, and receiver rotation angles with the radiographic isocenter contained within 8000 cm3 of the volumetric center of the CT volume. CONCLUSIONS: The investigated machine learning algorithm has the potential to aid surgeons in level localization, surgical planning, and intraoperative navigation through a completely automated 2D-3D registration process. Future work will focus on algorithmic optimizations to improve the convergence rate and speed profile.

Machine-Learning-Guided Discovery of 19F MRI Agents Enabled by Automated Copolymer Synthesis.

Modern polymer science suffers from the curse of multidimensionality. The large chemical space imposed by including combinations of monomers into a statistical copolymer overwhelms polymer synthesis and characterization technology and limits the ability to systematically study structure-property relationships. To tackle this challenge in the context of 19F magnetic resonance imaging (MRI) agents, we pursued a computer-guided materials discovery approach that combines synergistic innovations in automated flow synthesis and machine learning (ML) method development. A software-controlled, continuous polymer synthesis platform was developed to enable iterative experimental-computational cycles that resulted in the synthesis of 397 unique copolymer compositions within a six-variable compositional space. The nonintuitive design criteria identified by ML, which were accomplished by exploring <0.9% of the overall compositional space, lead to the identification of >10 copolymer compositions that outperformed state-of-the-art materials.

Comparison of single breath hyperpolarized 129 Xe MRI with dynamic 19 F MRI in cystic fibrosis lung disease.

PURPOSE: To quantitatively compare dynamic 19 F and single breath hyperpolarized 129 Xe MRI for the detection of ventilation abnormalities in subjects with mild cystic fibrosis (CF) lung disease. METHODS: Ten participants with stable CF and a baseline FEV1 > 70% completed a single imaging session where dynamic 19 F and single breath 129 Xe lung ventilation images were acquired on a 3T MRI scanner. Ventilation defect percentages (VDP) values between 19 F early-breath, 19 F maximum-ventilation, 129 Xe low-resolution, and 129 Xe high-resolution images were compared. Dynamic 19 F images were used to determine gas wash-in/out rates in regions of ventilation congruency and mismatch between 129 Xe and 19 F. RESULTS: VDP values from high-resolution 129 Xe images were greater than from low-resolution images (P = .001), although these values were significantly correlated (r = 0.68, P = .03). Early-breath 19 F VDP and max-vent 19 F VDP also showed significant correlation (r = 0.75, P = .012), with early-breath 19 F VDP values being significantly greater (P < .001). No correlation in VDP values were detected between either 19 F method or high-res 129 Xe images. In addition, the location and volume of ventilation defects were often different when comparing 129 Xe and 19 F images from the same subject. Areas of ventilation congruence displayed the expected ventilation kinetics, while areas of ventilation mismatch displayed abnormally slow gas wash-in and wash-out. CONCLUSION: In CF subjects, ventilation abnormalities are identified by both 19 F and HP 129 Xe imaging. However, these ventilation abnormalities are not entirely congruent. 19 F and HP 129 Xe imaging provide complementary information that enable differentiation of normally ventilated, slowly ventilated, and non-ventilated regions in the lungs.

Partially Fluorinated Copolymers as Oxygen Sensitive 19 F MRI Agents.

Effective diagnosis of disease and its progression can be aided by 19 F magnetic resonance imaging (MRI) techniques. Specifically, the inherent sensitivity of the spin-lattice relaxation time (T1 ) of 19 F nuclei to oxygen partial pressure makes 19 F MRI an attractive non-invasive approach to quantify tissue oxygenation in a spatiotemporal manner. However, there are only few materials with the adequate sensitivity to be used as oxygen-sensitive 19 F MRI agents at clinically relevant field strengths. Motivated by the limitations in current technologies, we report highly fluorinated monomers that provide a platform approach to realize water-soluble, partially fluorinated copolymers as 19 F MRI agents with the required sensitivity to quantify solution oxygenation at clinically relevant magnetic field strengths. The synthesis of a systematic library of partially fluorinated copolymers enabled a comprehensive evaluation of copolymer structure-property relationships relevant to 19 F MRI. The highest-performing material composition demonstrated a signal-to-noise ratio that corresponded to an apparent 19 F density of 220 mm, which surpasses the threshold of 126 mm 19 F required for visualization on a three Tesla clinical MRI. Furthermore, the T1 of these high performing materials demonstrated a linear relationship with solution oxygenation, with oxygen sensitivity reaching 240×10-5  mmHg-1 s-1 . The relationships between material composition and 19 F MRI performance identified herein suggest general structure-property criteria for the further improvement of modular, water-soluble 19 F MRI agents for quantifying oxygenation in environments relevant to medical imaging.

Initial clinical evaluation of stationary digital chest tomosynthesis in adult patients with cystic fibrosis.

OBJECTIVE: The imaging evaluation of cystic fibrosis currently relies on chest radiography or computed tomography. Recently, digital chest tomosynthesis has been proposed as an alternative. We have developed a stationary digital chest tomosynthesis (s-DCT) system based on a carbon nanotube (CNT) linear x-ray source array. This system enables tomographic imaging without movement of the x-ray tube and allows for physiological gating. The goal of this study was to evaluate the feasibility of clinical CF imaging with the s-DCT system. MATERIALS AND METHODS: CF patients undergoing clinically indicated chest radiography were recruited for the study and imaged on the s-DCT system. Three board-certified radiologists reviewed both the CXR and s-DCT images for image quality relevant to CF. CF disease severity was assessed by Brasfield score on CXR and chest tomosynthesis score on s-DCT. Disease severity measures were also evaluated against subject pulmonary function tests. RESULTS: Fourteen patients underwent s-DCT imaging within 72 h of their chest radiograph imaging. Readers scored the visualization of proximal bronchi, small airways and vascular pattern higher on s-DCT than CXR. Correlation between the averaged Brasfield score and averaged tomosynthesis disease severity score for CF was -0.73, p = 0.0033. The CF disease severity score system for tomosynthesis had high correlation with FEV1 (r = -0.685) and FEF 25-75% (r = -0.719) as well as good correlation with FVC (r = -0.582). CONCLUSION: We demonstrate the potential of CNT x-ray-based s-DCT for use in the evaluation of cystic fibrosis disease status in the first clinical study of s-DCT. KEY POINTS: • Carbon nanotube-based linear array x-ray tomosynthesis systems have the potential to provide diagnostically relevant information for patients with cystic fibrosis without the need for a moving gantry. • Despite the short angular span in this prototype system, lung features such as the proximal bronchi, small airways and pulmonary vasculature have improved visualization on s-DCT compared with CXR. Further improvements are anticipated with longer linear x-ray array tubes. • Evaluation of disease severity in CF patients is possible with s-DCT, yielding improved visualization of important lung features and high correlation with pulmonary function tests at a relatively low dose.

18F-3'-Deoxy-3'-Fluorothymidine Positron Emission Tomography Imaging for the Prediction of Acute Graft-Versus-Host Disease in Mouse Hematopoietic Stem Cell Transplant Models.

Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation. In mice, studies have demonstrated that donor conventional T cells traffic into host secondary lymphoid tissues early after transplant, and that this process is critical for the development of disease. As a result, the measurement of cellular proliferation within lymphoid sites early after transplant might be a useful approach for predicting aGVHD in humans. 18F-3'-deoxy-3'-fluorothymidine (FLT) positron emission tomography (PET) imaging has recently emerged as a functional imaging modality in oncology patients. FLT, a thymidine analog, is incorporated into replicating DNA and is thus an indirect marker of cellular proliferation. Here we report that FLT PET imaging can differentiate mice receiving alloreactive T cells and destined to develop lethal aGVHD from control mice. Mice receiving allogeneic T cells demonstrated a stronger FLT signal within the peripheral lymph nodes compared with control mice at all time points after transplant. In addition, allogeneic T cell recipients transiently demonstrated stronger FLT uptake within the spleen. Importantly, these differences were apparent before the development of clinical disease. In contrast, the FLT signal within the host bowel, an important aGVHD target organ, was more variable after transplant and was not consistently different between aGVHD mice and control mice. Collectively, these findings suggest that the imaging of patient lymphoid sites using existing FLT PET technology might be useful for predicting aGVHD in the clinical setting.

A method for evaluating the murine pulmonary vasculature using micro-computed tomography.

BACKGROUND: Significant mortality and morbidity are associated with alterations in the pulmonary vasculature. While techniques have been described for quantitative morphometry of whole-lung arterial trees in larger animals, no methods have been described in mice. We report a method for the quantitative assessment of murine pulmonary arterial vasculature using high-resolution computed tomography scanning. METHODS: Mice were harvested at 2 weeks, 4 weeks, and 3 months of age. The pulmonary artery vascular tree was pressure perfused to maximal dilation with a radio-opaque casting material with viscosity and pressure set to prevent capillary transit and venous filling. The lungs were fixed and scanned on a specimen computed tomography scanner at 8-µm resolution, and the vessels were segmented. Vessels were grouped into categories based on lumen diameter and branch generation. RESULTS: Robust high-resolution segmentation was achieved, permitting detailed quantitation of pulmonary vascular morphometrics. As expected, postnatal lung development was associated with progressive increase in small-vessel number and arterial branching complexity. CONCLUSIONS: These methods for quantitative analysis of the pulmonary vasculature in postnatal and adult mice provide a useful tool for the evaluation of mouse models of disease that affect the pulmonary vasculature.

Use of Susceptibility-Weighted Imaging (SWI) in the Detection of Brain Hemorrhagic Metastases from Breast Cancer and Melanoma.

PURPOSE: Susceptibility-weighted imaging (SWI) has significantly increased our sensitivity in detecting hemorrhagic brain lesions. We sought to explore the prevalence of intratumoral hemorrhage as detected by SWI in brain metastases from melanoma and breast cancer. METHODS: Lesions with a size of 0.1 cm were categorized as micrometastases, whereas larger lesions were categorized as macrometastases. Susceptibility-weighted imaging findings on locations corresponding to enhancing lesions were categorized as either positive or negative based on presence/absence of signal dropout. The percentage of SWI positivity was then estimated as a function of lesion size. Two-tailed Fisher exact test was performed to examine differences in the contingency tables. RESULTS: Magnetic resonance imaging studies from 73 patients with 1173 brain metastases, which enhanced on postcontrast T1-weighted imaging (T1WI) were selected for analysis. Of these lesions, 952 had SWI data available, and 342 of 952 were micrometastases. Only 10 of the 342 micrometastases and 410 (67.2%) of the 610 macrometastases were SWI positive (P < 0.0001). When examined by tumor type, 76.9% (melanoma) versus 55.6% (breast cancer) were SWI positive (P < 0.0001), regardless of tumor size. All melanoma lesions (8/8) and only 1 of 15 breast cancer lesions larger than 1.5 cm were SWI positive. CONCLUSION: With the use of combined SWI and contrast-enhanced high-resolution T1 imaging, we found that presence of intratumoral brain hemorrhage is uncommon in micrometastases but common in metastases greater than 0.1 cm from breast cancer or melanoma. Large metastases commonly harbored hemorrhage, and this occurred more frequently in patients with melanoma than with breast cancer.

Sonographic Characterization of Arterial Dissections in Takayasu Arteritis.

OBJECTIVES: Takayasu arteritis is a relatively rare chronic nonspecific form of large-vessel vasculitis in which the involved vessels develop stenoses, occlusions, dilatations or aneurysms, and dissections. Dissections of the arteries in patients with Takayasu arteritis are not well understood. In this study, we explored the sonographic characterization of these rare complications secondary to Takayasu arteritis. METHODS: We evaluated arterial dissections in 72 patients with a clinical diagnosis of Takayasu arteritis by vascular sonography and transthoracic echocardiography. We analyzed the dissection distribution and morphologic characteristics of the dissected intima/layer and lumen of the involved vessels. RESULTS: Twelve of 72 patients had arterial dissections, in whom 16 dissected segments were identified. The involved arteries included the carotid, subclavian, vertebral, brachial, celiac, and femoral arteries, aortic arch, and abdominal aorta. The dissection lesions occurred at any age and coexisted with the aforementioned injuries. Evaluation of the dissected intima/layer and the involved lumen by sonography was technically complicated. The morphologic characteristics of the dissected intimae and involved lumens were complex, with most of the dissected intimae/layers having the characteristic "macaroni" sign in the arterial wall. High-frequency and high-resolution sonography, color Doppler flow imaging, and other techniques were useful in elucidating greater lesion details. CONCLUSIONS: Arterial dissections in Takayasu arteritis can involve any anatomic vessel location and have complex morphologic characteristics. Sonography is the optimal technique for diagnosis and follow-up of patients with Takayasu arteritis and dissections.

Sonography and Transthoracic Echocardiography for Diagnosis of Systemic Cardiovascular Metastatic Tumor Thrombi.

Sonography and transthoracic echocardiography (TTE) are seldom used for assessment of metastatic tumor thrombi in the cardiovascular system in routine clinical practice. We performed this retrospective study to evaluate the combination of sonography with TTE for diagnosis of metastatic tumor thrombi in heart and systemic vessels. Vascular, abdominal, pelvic, and small-part sonography was applied in 18 patients, and TTE was conducted simultaneously in 14 patients. Tumor thrombi invaded into the inferior vena cava system in 12 patients, superior vena cava system in 5 patients, and aorta in 1 patient; they extended to the right cardiac chambers in 11 patients. Six patients had diagnoses by pathologic examination. The primary neoplasms were identified by conventional imaging in 17 patients. The morphologic and echogenic characteristics of the tumor thrombi were diverse and depended on their original tumors. The thrombi were either contiguous or discrete from the original tumors. The neoplastic vascularity of the thrombi and the invasive extension were the primary characteristics that distinguished them from bland thrombi. Simultaneous application of sonography and TTE is a feasible way to comprehensively evaluate cardiovascular metastatic tumor thrombi in most patients.

Probabilistic Air Segmentation and Sparse Regression Estimated Pseudo CT for PET/MR Attenuation Correction.

PURPOSE: To develop a positron emission tomography (PET) attenuation correction method for brain PET/magnetic resonance (MR) imaging by estimating pseudo computed tomographic (CT) images from T1-weighted MR and atlas CT images. MATERIALS AND METHODS: In this institutional review board-approved and HIPAA-compliant study, PET/MR/CT images were acquired in 20 subjects after obtaining written consent. A probabilistic air segmentation and sparse regression (PASSR) method was developed for pseudo CT estimation. Air segmentation was performed with assistance from a probabilistic air map. For nonair regions, the pseudo CT numbers were estimated via sparse regression by using atlas MR patches. The mean absolute percentage error (MAPE) on PET images was computed as the normalized mean absolute difference in PET signal intensity between a method and the reference standard continuous CT attenuation correction method. Friedman analysis of variance and Wilcoxon matched-pairs tests were performed for statistical comparison of MAPE between the PASSR method and Dixon segmentation, CT segmentation, and population averaged CT atlas (mean atlas) methods. RESULTS: The PASSR method yielded a mean MAPE ± standard deviation of 2.42% ± 1.0, 3.28% ± 0.93, and 2.16% ± 1.75, respectively, in the whole brain, gray matter, and white matter, which were significantly lower than the Dixon, CT segmentation, and mean atlas values (P < .01). Moreover, 68.0% ± 16.5, 85.8% ± 12.9, and 96.0% ± 2.5 of whole-brain volume had within ±2%, ±5%, and ±10% percentage error by using PASSR, respectively, which was significantly higher than other methods (P < .01). CONCLUSION: PASSR outperformed the Dixon, CT segmentation, and mean atlas methods by reducing PET error owing to attenuation correction.

Effects of raltegravir combined with tenofovir/emtricitabine on body shape, bone density, and lipids in African-Americans initiating HIV therapy.

BACKGROUND: Raltegravir (RAL) plus tenofovir/emtricitabine (TDF/FTC) is a recommended initial antiretroviral regimen. A substantial proportion of persons diagnosed with HIV infection and starting antiretrovirals in the U.S. are African-American (AA); however, the effects of this regimen on metabolic parameters have largely been studied in white patients. METHODS: Single-arm, open-label study of untreated AA HIV-infected patients administered RAL with TDF/FTC for 104 weeks. Changes in fasting lipids, insulin resistance, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), limb and trunk fat, and bone mineral density (BMD) were assessed at weeks 56 and 104. RESULTS: Thirty (85% men) participants were included. Median entry characteristics included age of 38 years, CD4 323 cells/mm3, HIV RNA level 29,245 copies/ml, and body mass index 28.1 kg/m2. At 56 and 104 weeks, significant increases in VAT, trunk fat, limb fat, and overall fat were observed. Bone mineral density decreased by 1.5% by week 104.There were no significant changes in non-HDL-cholesterol, fasting triglycerides, or insulin resistance. A median CD4 cell count increase of 318 cells/mm3 (IQR 179, 403; full range 40, 749) (P<0.001) was observed. Assuming missing=failure, 78 and 70% had HIV RNA levels<40 copies/ml at weeks 56 and 104, respectively. There were no treatment-related discontinuations and no new antiretroviral resistance mutations were detected. CONCLUSIONS: In this cohort of AAs, initiation of RAL with TDF/FTC was associated with significant general increases in fat. Significant changes in lipids or insulin resistance were not observed and there was a small decline in BMD. Therapy was well tolerated and effective. These results are consistent with findings of studies of initial antiretroviral therapy in racially diverse cohorts and inform treatment selection for AA patients starting therapy for HIV infection.

A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy.

OBJECTIVE: Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Phase I trial of infants undergoing therapeutic hypothermia for HIE receiving IV caffeine 20 mg/kg followed by up to two daily doses of 5 mg/kg (n = 9) or 10 mg/kg (n = 8). Safety was evaluated based on adverse events and frequency of pre-specified outcomes compared to data from the Whole-Body Hypothermia for HIE trial (Shankaran, 2005). RESULTS: Twelve of 17 (71%) infants had ≥1 adverse event during the study period. The frequency of clinical outcomes related to HIE were not statistically different from outcomes in infants receiving hypothermia in the Whole-Body Hypothermia for HIE trial. CONCLUSION: Caffeine administration was well tolerated. A larger study is required to determine the optimal dose and evaluate drug safety and efficacy. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT03913221.

Stationary prospective cardiac gated computed tomography-dynamic study in phantoms andin vivo.

Objective.This study explores the feasibility of a stationary gantry cardiac gated computed tomography (CT) with carbon nanotube (CNT) linear x-ray source arrays.Approach.We developed a stationary gantry CT system utilizing multipixel CNT x-ray sources. Given the advantages of straightforward x-ray pulse control with these sources, we investigated the potential for gated prospective imaging. We implemented prospective respiratory and cardiac gating control and evaluated the system through dynamic phantom imaging studies followed by imaging of a porcine model.Main Results.The findings revealed minimal anatomical motion artifacts in the heart and lungs, confirming successful physiologic gated acquisition in stationary gantry cardiac CT. This indicates the potential of this imaging approach for reducing artifacts and improving image quality.Significance.This study demonstrates the feasibility of prospective physiological gating with CNT x-ray sources in a stationary gantry setup for cardiac imaging. This approach could potentially alleviate the need for beta blocker administration during cardiac CT scans, thereby increasing the flexibility of the imaging system and enabling the imaging of a wider variety of patient cardiac conditions.

Improving the accuracy of bone mineral density using a multisource CBCT.

Multisource cone beam computed tomography CBCT (ms-CBCT) has been shown to overcome some of the inherent limitations of a conventional CBCT. The purpose of this study was to evaluate the accuracy of ms-CBCT for measuring the bone mineral density (BMD) of mandible and maxilla compared to the conventional CBCT. The values measured from a multi-detector CT (MDCT) were used as substitutes for the ground truth. An anthropomorphic adult skull and tissue equivalent head phantom and a homemade calibration phantom containing inserts with varying densities of calcium hydroxyapatite were imaged using the ms-CBCT, the ms-CBCT operating in the conventional single source CBCT mode, and two clinical CBCT scanners at similar imaging doses; and a clinical MDCT. The images of the anthropomorphic head phantom were reconstructed and registered, and the cortical and cancellous bones of the mandible and the maxilla were segmented. The measured CT Hounsfield Unit (HU) and Greyscale Value (GV) at multiple region-of-interests were converted to the BMD using scanner-specific calibration functions. The results from the various CBCT scanners were compared to that from the MDCT. Statistical analysis showed a significant improvement in the agreement between the ms-CBCT and MDCT compared to that between the CBCT and MDCT.

A carbon nanotube x-ray source array designed for a new multisource cone beam computed tomography scanner.

Cone beam computed tomography (CBCT) is known to suffer from strong scatter and cone beam artifacts. The purpose of this study is to develop and characterize a rapidly scanning carbon nanotube (CNT) field emission x-ray source array to enable a multisource CBCT (ms-CBCT) image acquisition scheme which has been demonstrated to overcome these limitations. A CNT x-ray source array with eight evenly spaced focal spots was designed and fabricated for a medium field of view ms-CBCT for maxillofacial imaging. An external multisource collimator was used to confine the radiation from each focal spot to a narrow cone angle. For ms-CBCT imaging, the array was placed in the axial direction and rapidly scanned while rotating continuously around the object with a flat panel detector. The x-ray beam profile, temporal and spatial resolutions, energy and dose rate were characterized and evaluated for maxillofacial imaging. The CNT x-ray source array achieved a consistent focal spot size of 1.10 ± 0.04 mm × 0.84 ± 0.03 mm and individual beam cone angle of 2.4°±0.08 after collimation. The x-ray beams were rapidly switched with a rising and damping times of 0.21 ms and 0.19 ms, respectively. Under the designed operating condition of 110 kVp and 15 mA, a dose rate of 8245µGy s-1was obtained at the detector surface with the inherent Al filtration and 2312µGy s-1with an additional 0.3 mm Cu filter. There was negligible change of the x-ray dose rate over many operating cycles. A ms-CBCT scan of an adult head phantom was completed in 14.4 s total exposure time for the imaging dose in the range of that of a clinical CBCT scanner. A spatially distributed CNT x-ray source array was designed and fabricated. It has enabled a new multisource CBCT to overcome some of the main inherent limitations of the conventional CBCT.

Uterine Uptake of Estrogen and Progestogen-Based Radiotracers in Rhesus Macaques with Endometriosis.

PURPOSE: Endometriosis is an estrogen-dependent disorder of menstruating primates where tissues similar to the inner lining of the uterus exist "ectopically" outside of the uterus. The ectopic endometrium, like the endometrium within the uterus, expresses estrogen receptors (ER) and progesterone receptors (PR) and undergoes hormone-dependent cell proliferation and bleeding each menstrual cycle. The goal of this study was to conduct abdominopelvic positron emission tomography (PET) scans with computed tomography (CT) imaging of rhesus macaques (Macaca mulatta) using radiotracers that target ER and PR [16α-[18F]fluoroestradiol (FES) and 12-[18F]fluoro-furanyl-nor-progesterone (FFNP)] in individuals with and without endometriosis. We also aimed to determine if menstrual cycle phase and/or the presence of endometriosis affected the uptake of these radiotracers. PROCEDURES: Rhesus macaques with either clinically diagnosed endometriosis (n = 6) or no endometriosis (n = 4) underwent PET/CT scans with FES. A subset of the animals also underwent PET/CT scans with FFNP. Standard uptake values corrected for body weight (SUVs) were obtained for each radiotracer in target and background tissues (e.g., intestinal). We performed repeated measure analysis of variance tests to determine how uterine and background uptake differed with scan time, phase of the menstrual cycle, and disease state. RESULTS: Abdominopelvic PET/CT could not resolve small, individual endometriotic lesions. However, macaques with endometriosis displayed higher uterine uptake compared to those without the disorder. Radiotracer uptake differed by menstrual cycle phase with increased uterine uptake of both radiotracers in the proliferative phase of the menstrual cycle. Background intestinal uptake of FFNP increased over time after infusion, but only during the proliferative phase. CONCLUSIONS: PET/CT with FES and FFNP support the concept that ER and PR levels are altered in individuals with endometriosis. This highlights the impact of the disease on typical reproductive tract function and may provide a novel pathway for the identification of individuals with endometriosis.

Fluoroestradiol PET-MRI imaging for detection of endometriosis lesions and symptom correlation.

Endometriosis is a common cause of infertility, pelvic pain, and dysmenorrhea and there are prior case reports of lesion detection using an 18F-fluoroestradiol (FES) tracer with positron emission tomography (PET). We aimed to further investigate the use of the FES tracer in the context of PET-magnetic resonance (PET-MR) imaging. We administered FES to 6 patients and then imaged them using a Siemens mMR PET-MR scanner. Each patient was taken to surgery within 30 days after imaging, and surgical visualization served as the gold-standard for diagnosis. PET did not prove to be as sensitive as MR (50% per-patient sensitivity versus 67% per-patient and 35% versus 48% per-lesion), and did not show any additional sites over and above MR. When MR was used to localize lesions on PET after imaging, there was insufficient evidence of an association between total tracer uptake and reported pain intensity (P=0.25). FES PET-MR offers no additional value to MR for endometriosis.