PySupercharge: a python algorithm for enabling ABC transporter bacterial secretion of all proteins through amino acid mutation.

BACKGROUND: The process of producing proteins in bacterial systems and secreting them through ATP-binding cassette (ABC) transporters is an area that has been actively researched and used due to its high protein production capacity and efficiency. However, some proteins are unable to pass through the ABC transporter after synthesis, a phenomenon we previously determined to be caused by an excessive positive charge in certain regions of their amino acid sequence. If such an excessive charge is removed, the secretion of any protein through ABC transporters becomes possible. RESULTS: In this study, we introduce 'linear charge density' as the criteria for possibility of protein secretion through ABC transporters and confirm that this criterion can be applied to various non-secretable proteins, such as SARS-CoV-2 spike proteins, botulinum toxin light chain, and human growth factors. Additionally, we develop a new algorithm, PySupercharge, that enables the secretion of proteins containing regions with high linear charge density. It selectively converts positively charged amino acids into negatively charged or neutral amino acids after linear charge density analysis to enable protein secretion through ABC transporters. CONCLUSIONS: PySupercharge, which also minimizes functional/structural stability loss of the pre-mutation proteins through the use of sequence conservation data, is currently being operated on an accessible web server. We verified the efficacy of PySupercharge-driven protein supercharging by secreting various previously non-secretable proteins commonly used in research, and so suggest this tool for use in future research requiring effective protein production.

The natural history of celiac artery aneurysms.

OBJECTIVES: The goal of this study was to document the natural history of celiac artery aneurysms (CAAs). BACKGROUND: Celiac artery aneurysms are rare. Existing literature is skewed towards outcomes after intervention of large, symptomatic aneurysms but the behavior of untreated CAAs is poorly understood. METHODS: This is a single institution, retrospective analysis of patients with CAA diagnosed by CT imaging (2015-2019) identified through an institutional radiology database. Radiologic, demographic, and follow-up data were analyzed. The primary endpoint was the mean growth rate of CAAs. RESULTS: Of the 76 patients included, 86.8% were men with a mean age at presentation of 69.8 years. The mean CAA diameter on index imaging was 15.4 +/- 3.8 mm (range, 7-30 mm). All were classified as true aneurysms and 76.3% were saccular. All patients had clinical follow-up with mean follow-up 31.2 months +/- 21.6 months. No patient developed symptoms or rupture. The mean radiological follow-up among 45 patients was 25.2 +/- 16.8 months. Over this period, 16 CAAs (35.6%) enlarged, while 29 (64.4%) remained stable. One patient (1.3%) underwent intervention for increasing size in the setting of a chronic dissection. On multivariate analysis, age <70 was significantly associated with increased risk of aneurysm growth. CONCLUSIONS: In this institutional review of patients with CAAs, the majority of aneurysms remained stable in size, with no patients developing symptoms or rupture over clinical follow-up. Given the observed benign behavior of these aneurysms, guidelines that suggest conservative management of CAAs less than 2 cm seems appropriate.

Natural history of renal artery aneurysms.

OBJECTIVE: The existing renal artery aneurysm (RAA) literature is largely composed of reports of patients who underwent intervention. The objective of this study was to review the natural history of RAA. METHODS: This single-institution retrospective analysis studied all patients with RAA diagnosed by computed tomography imaging between 2015 and 2019, identified by our institutional radiology database. Imaging, demographic, and clinical data were obtained via the electronic medical record. He growth rate was calculated for all patients with radiological follow-up. RESULTS: The cohort consists of 331 patients with 338 RAAs. Most patients were female (61.3%), with 11 (3.3%) of childbearing age. The mean age at diagnosis was 71.5 years (range, 24-99 years). Medical comorbidities included hypertension (73.7%), prior smoking (34.4%), and connective tissue disease (3.9%). Imaging indications included abdominal pain (33.5%), unrelated follow-up (29.6%), and follow-up of an RAA initially diagnosed before the study period (10.7%). Right RAA (61.9%) was more common than left (35.1%); 3% of patients had bilateral RAA. The mean diameter at diagnosis was 12.9 ± 5.9 mm. Size distribution included lesions measuring less than <15 mm (69.9%), 15 to 25 mm (27.1%), and more than 25 mm (3.0%). Anatomic locations included the distal RA (26.7%), renal hilum (42.4%), and mid-RA (13.1%). The majority were true aneurysms (98%); of these, 72.3% were fusiform and 27.7% were saccular. Additional characteristics included calcification (82.2%), thrombus (15.9%), and dissection (0.9%). Associated findings included aortic atherosclerosis (65.6%), additional visceral aneurysms (7.3%), and abdominal aortic aneurysm (5.7%). The mean clinical follow-up among 281 patients was 41.0 ± 24.0 months. The mean radiological follow-up among 137 patients was 26.0 ± 21.4 months. Of these, 43 patients (31.4%) experienced growth, with mean growth rate of 0.23 ± 4.7 mm/year; the remainder remained stable in size. Eight patients eventually underwent intervention (5 endovascular), with the most common indications including size criteria (4/8) and symptom development (3/8). No patient developed rupture. On multivariate analysis, obesity (P = .04) was significantly associated with growth. An initial diameter of more than 25 mm was significantly associated with subsequent intervention (P = .006), but was not significantly associated with growth. Four of five RAAs with an initial diameter 30 mm or greater did not undergo intervention. The mean clinical follow-up for these patients was 24 months; none developed rupture and two remained stable in size. CONCLUSIONS: This large institutional cohort found that the majority of RAAs remained stable in size, with few patients meeting indications for repair based on societal guidelines. Current guidelines recommending intervention for asymptomatic aneurysms more than 30 mm seem to be appropriate given their slow progression.

Hypercoagulability in Patients With Coronavirus Disease (COVID-19): Identification of Arterial and Venous Thromboembolism in the Abdomen, Pelvis, and Lower Extremities.

The purpose of this article is to describe arterial and venous thromboembolism in the abdomen, pelvis, and lower extremities in patients with coronavirus disease (COVID-19). Eighty-two patients with COVID-19 who underwent abdominal ultrasound or CT were retrospectively compared with 82 patients without COVID-19 for thromboembolism and solid-organ infarction. Nine (11%) patients with COVID-19 had thromboembolic findings, with medium to large arterial thrombi in five. One patient without COVID-19 had known portal vein thrombus on CT. Thromboembolic findings occurred more frequently in patients with than without COVID-19 (p = 0.02).

White matter but not grey matter predicts change in reading skills after intervention.

This study examined changes in white matter microstructure and grey matter volume, cortical thickness, and cortical surface area before and after reading intervention. Participants included 22 average readers and 13 dyslexic readers (8-9 years old in third grade); the dyslexic readers were enrolled in reading intervention programs at their elementary school. Participants completed scans of diffusion tensor imaging and T1-weighted MRI before and after 3 months of instruction. An a priori region of interest (ROI) analysis was used. Dyslexic readers, compared to average readers, showed higher mean diffusivity in white matter ROIs including bilateral inferior frontal, bilateral insula, left superior temporal, and right supramarginal gyri across time points. Dyslexic readers also had thicker cortex in left fusiform and bilateral supramarginal gyri; whereas, average readers had greater surface area in right fusiform across time. There were no significant changes in white or grey matter following intervention; however, mean diffusivity in the right hemisphere was associated with reading gains over time. White matter organization in the right hemisphere predicts reading changes, and dyslexic readers may have persistent differences in white and grey matter due to ongoing reading deficits.

Unexpected Findings of Coronavirus Disease (COVID-19) at the Lung Bases on Abdominopelvic CT.

OBJECTIVE. The purpose of this study is to report unanticipated lung base findings on abdominal CT in 23 patients concerning for coronavirus disease (COVID-19). In these patients, who were not previously suspected of having COVID-19, abdominal pain was the most common indication for CT (n = 19), and 11 patients had no extrapulmonary findings. Seventeen patients underwent polymerase chain reaction testing, which returned positive results for all 17. CONCLUSION. Unsuspected coronavirus disease may be strongly suggested on the basis of lung findings on abdominopelvic CT.

Natural History, Clinical Significance, and the Role of Vascular Referral in the Management of Penetrating Ulcers of the Abdominal Aorta.

BACKGROUND: Penetrating ulcers of the abdominal aorta (PUAA) are an increasingly common finding on abdominal imaging studies; however, their significance and natural history are not well described. This study's objective was to analyze the demographics, presentation, and outcomes of patients with a radiographic diagnosis of PUAA. MATERIALS AND METHODS: Patients at our tertiary referral center were identified for inclusion based on a search for the term "penetrating ulcer" in abdominal computed tomography and magnetic resonance imaging reports between January 2014 and December 2017. Patients' electronic medical records were retrospectively reviewed to determine baseline medical characteristics, imaging indication, and subsequent clinical course, interventions, and outcomes. Aortic diameters and ulcer depths were measured by a single observer on initial and follow-up imaging to assess for association with concomitant aortic pathology, evolving aortic disease, and ulcer progression, defined as increase in depth of ≥ 1 mm. Statistical analysis was performed using STATA 16 (College Station, TX: StataCorp LLC), and a threshold P-value of <0.05 was set for significance. RESULTS: Ninety-two patients with PUAA were identified; 57 (62%) were male. The mean age at diagnosis was 79.3 years, and comorbidities included hypertension (74%), hyperlipidemia (65%), and malignancy (34%). The most common indication for imaging was chest, back, or abdominal pain (19%). On initial imaging, the mean ulcer depth was 1 cm (range from 0.2 cm to 3.4 cm). Concomitant abdominal aortic dilation ≥ 3 cm was found in 34 (37%) patients. Thirty-six (39%) patients had a vascular surgery consultation immediately after radiographic diagnosis. Follow-up axial imaging was performed on 27 (29%) untreated patients. The overall sample's mean ulcer depth remained essentially unchanged from initial measurement (P = 0.99); however, 14 (52%) patients with follow-up imaging were found to have increased overall aortic diameter. Of the total 92 patients, 9 (10%) underwent an endovascular abdominal aortic intervention during the review period: 2 for symptomatic PUAA and the remainder for progression of concomitant aneurysmal disease. All-cause mortality was 5% during the mean follow-up period of 21.9 months (range 0 to 72.5 months). Of the patients lost to follow-up, 61% did not receive vascular referral after initial diagnosis. CONCLUSIONS: PUAA are typically incidental findings identified in elderly, comorbid patients undergoing imaging for an unrelated indication. Although isolated findings of asymptomatic PUAA rarely require surgical intervention, these patients we argue would benefit from vascular surgery referral for long-term follow-up and interval imaging to assess for disease progression and concomitant aortic degeneration, which may necessitate repair. In addition, we observed that most of those patients lost to follow-up did not receive vascular consultation, suggesting that lack of involvement of vascular specialists at the time of diagnosis is a missed opportunity to secure appropriate follow-up and management.

Downstream Costs Associated With Incidental Pancreatic Cysts Detected at MRI.

OBJECTIVE: The purpose of this study is to assess downstream costs associated with pancreatic cysts incidentally detected at MRI. MATERIALS AND METHODS: Two hundred patients with an incidental pancreatic cyst detected at MRI were identified. Downstream events (imaging, office visits, endoscopic ultrasound-guided fine-needle aspiration, or chemotherapy) were identified from the electronic medical record. Radiologists' recommendations and ordering physician management were classified relative to the American College of Radiology (ACR) incidental findings committee recommendations. Costs for the downstream events were estimated using national Medicare rates and a 3% annual discount rate. Mean costs were computed. RESULTS: Estimated downstream costs averaged $460 per cyst ($872 per cyst with any follow-up testing). Nine patients had a clinically relevant outcome during follow-up (increase in cyst size, development of new cyst, or development of pancreatic cancer). Downstream cost per cyst with a clinically relevant outcome was $1364. Costs were greater when ordering physicians overmanaged ($842) versus when they were adherent ($631) or undermanaged ($252) relative to radiologist recommendation. Although costs were $252 when ordering physicians undermanaged relative to ACR incidental findings committee recommendations, costs were similar when ordering physicians were adherent ($811) or overmanaged ($845) relative to ACR incidental findings committee recommendations. Costs did not vary significantly according to whether radiologists recommended follow-up testing ($317-$491) or whether radiologist recommendations were adherent, undermanaged, or overmanaged relative to ACR incidental findings committee recommendations ($344-$528). CONCLUSION: The findings suggest a role for targeted educational efforts, collaborative partnerships, and other initiatives to foster greater adherence to radiologist recommendations, including critical test results notification systems, automated reminders within electronic health systems, and stronger language within radiology reports when no follow-up testing is recommended.

Informatics Solutions for Driving an Effective and Efficient Radiology Practice.

Radiologists are facing increasing workplace pressures that can lead to decreased job satisfaction and burnout. The increasing complexity and volumes of cases and increasing numbers of noninterpretive tasks, compounded by decreasing reimbursements and visibility in this digital age, have created a critical need to develop innovations that optimize workflow, increase radiologist engagement, and enhance patient care. During their workday, radiologists often must navigate through multiple software programs, including picture archiving and communication systems, electronic health records, and dictation software. Furthermore, additional noninterpretive duties can interrupt image review. Fragmented data and frequent task switching can create frustration and potentially affect patient care. Despite the current successful technological advancements across industries, radiology software systems often remain nonintegrated and not leveraged to their full potential. Each step of the imaging process can be enhanced with use of information technology (IT). Successful implementation of IT innovations requires a collaborative team of radiologists, IT professionals, and software programmers to develop customized solutions. This article includes a discussion of how IT tools are used to improve many steps of the imaging process, including examination protocoling, image interpretation, reporting, communication, and radiologist feedback. ©RSNA, 2018.

Nonlocal Nuclear Spin Quieting in Quantum Dot Molecules: Optically Induced Extended Two-Electron Spin Coherence Time.

We demonstrate the extension of coherence between all four two-electron spin ground states of an InAs quantum dot molecule (QDM) via nonlocal suppression of nuclear spin fluctuations in two vertically stacked quantum dots (QDs), while optically addressing only the top QD transitions. Long coherence times are revealed through dark-state spectroscopy as resulting from nuclear spin locking mediated by the exchange interaction between the QDs. Line shape analysis provides the first measurement of the quieting of the Overhauser field distribution correlating with reduced nuclear spin fluctuations.

Patient Recall Imaging in the Ambulatory Setting.

OBJECTIVE: Recalling a patient to repeat a radiology examination is an adverse and, in certain cases, preventable event. Our objectives were to assess the rate of patient recalls for all imaging performed in the outpatient setting at our institution and to characterize the underlying reasons for the recalls. MATERIALS AND METHODS: We performed a retrospective review of all repeat imaging requests for an inadequate initial imaging study between January 2012 and March 2015. RESULTS: We identified 100 recall requests (mean, 2.6 requests per month), for an overall recall rate of approximately 1 in 8046 ambulatory studies and 1 in 1684 MRI studies. Nearly all recalls (98%) involved adults. A total of 95% of the recalls were for MRI studies. The most common reason for a patient recall request was an incomplete examination, making up 24% of all requests. The other causes were inadequate coverage of the area of interest (22%), protocoling errors (20%), poor imaging quality (15%), additional imaging to clarify a finding (11%), insufficient contrast visualization (7%), and incorrect patient information (1%). CONCLUSION: We found that patient recalls for imaging in the outpatient setting at our institution are not common. When recalls did occur, they were most often related to the acquisition of MR images. Improved technologist education on MRI protocoling and enhanced communication between ordering clinicians and radiologists to clarify the purpose of imaging might reduce the need for repeat ambulatory imaging.

Molecularly Designed Stabilized Asymmetric Hollow Fiber Membranes for Aggressive Natural Gas Separation.

New rigid polyimides with bulky CF3 groups were synthesized and engineered into high-performance hollow fiber membranes. The enhanced rotational barrier provided by properly positioned CF3 side groups prohibited fiber transition layer collapse during cross-linking, thereby greatly improving CO2 /CH4 separation performance compared to conventional materials for aggressive natural gas feeds.

MDCT diagnosis of acute pulmonary embolism in the emergent setting.

To compare utilization of CT pulmonary angiogram (CTA) for diagnosis of pulmonary embolism (PE) in an emergency department (ED) with unstructured CT ordering to published rates of CT positivity in other EDs including those employing decision support and to identify pathways for improved utilization via collaboration with our pathology and ED colleagues. Two hundred seventeen patients over a 2.5-month time period who received a CTA for PE were reviewed with exclusion of pediatric patients and all sub-optimal, non-diagnostic, or equivocal scans; 21 were excluded leaving a sample of 196 patients. The rate of PE diagnosis and association of PE positivity with selected factors (D-dimer testing) was assessed. The percentage of cases positive for PE was 10.7 % (21/196) which is similar to the frequently published rate of 10 % in other emergency departments including settings that have studied the use of decision support. D-dimer testing was performed in 40.3 % of cases. In 29.6 % (58/196) of subjects, D-dimer was positive, 10.7 % (21/196) was negative, and 59.7 % (117/196) was not assessed. Prevalence of PE among D-dimer negative (0 %, 0/21) was lower versus positive D-dimer (12.1 %, 7/58) and unknown D-dimer patients (12.0 %, 14/117). D-dimer had 100 % (21/21) negative predictive value for the diagnosis of PE. While this suggests that D-dimer is useful to rule-out PE, due to the small number of patients with PE, the 95 % confidence intervals are wide and the post-test likelihood of PE could be as high as 14 %. The rate of CT positivity for PE in an ED with unstructured CT ordering is similar to that in other published series including as series in which decision support was used. While D-dimer had high negative predictive value, large studies are needed to confirm this high sensitivity and potentially increase its use in ruling out PE without CT and to reduce CT ordering particularly in patients with sufficiently low clinical pre-test probability of PE.

Batf3+ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy.

The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8+ T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3+ DCs and CD8+ T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3+ DCs within the TME is associated with CD8+ T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3+ DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4-1BB/4-1BB ligand (4-1BBL) axis during this process.

Reducing false-positive biopsies: a pilot study to reduce benign biopsy rates for BI-RADS 4A/B assessments through testing risk stratification and new thresholds for intervention.

The aim of this study is to evaluate Breast Imaging Reporting and Data Systems (BI-RADS) 4A/B subcategory risk estimates for ductal carcinoma in situ (DCIS) and invasive cancer (IC), determining whether changing the proposed cutoffs to a higher biopsy threshold could safely increase cancer-to-biopsy yields while minimizing false-positive biopsies. A prospective clinical trial was performed to evaluate BI-RADS 4 lesions from women seen in clinic between January 2006 and March 2007. An experienced radiologist prospectively estimated a percent risk-estimate for DCIS and IC. Truth was determined by histopathology or 4-year follow-up negative for malignancy. Risk estimates were used to generate receiver-operating characteristic (ROC) curves. Biopsy rates, cancer-to-biopsy yields, and type of malignancies missed were then calculated across postulated risk thresholds. A total of 124 breast lesions were evaluated from 213 women. An experienced radiologist gave highly accurate risk estimates for IC, DCIS alone, or the combination with an area under ROC curve of 0.91 (95 % CI 0.84-0.99) (p < 0.001), 0.81 (95 % CI 0.69-0.93) (p = 0.011), and 0.89 (95 % CI 0.83-0.95) (p < 0.001), respectively. The cancer-to-biopsy yield was 30 %. Three hypothetical thresholds for intervention were analyzed: (1) DCIS or IC ≥ 10 %; (2) DCIS ≥ 50 % or IC ≥ 10 %; and (3) IC ≥ 10 %, which translated to 22, 48, and 56 % of biopsies avoided; cancer-to-biopsy yields of 36, 47, and 46 %; and associated chance of missing an IC of 0, 1, and 2 %, respectively. Expert radiologists estimate risk of IC and DCIS with a high degree of accuracy. Increasing the cut off point for recommending biopsy, substituting with a short-term follow-up protocol with biopsy if any change, may safely reduce the number of false-positive biopsies.

Comparison of nonenhanced MR angiographic subtraction techniques for infragenual arteries at 1.5 T: a preliminary study.

PURPOSE: To evaluate diagnostic performance of three nonenhanced methods: variable-refocusing-flip angle (FA) fast spin-echo (SE)-based magnetic resonance (MR) angiography (variable FA MR) and constant-refocusing-FA fast SE-based MR angiography (constant-FA MR) and flow-sensitive dephasing (FSD)-prepared steady-state free precession MR angiography (FSD MR) for calf arteries, with dual-injection three-station contrast material-enhanced MR angiography (gadolinium-enhanced MR) as reference. MATERIALS AND METHODS: This prospective study was institutional review board approved and HIPAA compliant, with informed consent. Twenty-one patients (13 men, eight women; mean age, 62.6 years) underwent calf-station variable-FA MR, constant-FA MR, and FSD MR at 1.5 T, with gadolinium-enhanced MR as reference. Image quality and stenosis severity were assessed in 13 segments per leg by two radiologists blinded to clinical data. Combined constant-FA MR and FSD MR reading was also performed. Methods were compared (logistic regression for correlated data) for diagnostic accuracy. RESULTS: Of 546 arterial segments, 148 (27.1%) had a hemodynamically significant (≥ 50%) stenosis. Image quality was satisfactory for all nonenhanced MR sequences. FSD MR was significantly superior to both other sequences (P < .0001), with 5-cm smaller field of view; 9.6% variable-FA MR, 9.6% constant-FA MR, and 0% FSD MR segmental evaluations had nondiagnostic image quality scores, mainly from high diastolic flow (variable-FA MR) and motion artifact (constant-FA MR). Stenosis sensitivity and specificity were highest for FSD MR (80.3% and 81.7%, respectively), compared with those for constant-FA MR (72.3%, P = .086; and 81.8%, P = .96) and variable-FA MR (75.9%, P = .54; and 75.6%, P = .22). Combined constant-FA MR and FSD MR had superior sensitivity (81.8%) and specificity (88.3%) compared with constant-FA MR (P = .0076), variable-FA MR (P = .0044), and FSD MR (P = .0013). All sequences had an excellent negative predictive value (NPV): 93.2%, constant-FA MR; 94.7%, variable-FA MR; 91.7%, FSD MR; and 92.9%, combined constant-FA MR and FSD MR. CONCLUSION: At 1.5 T, all evaluated nonenhanced MR angiographic methods demonstrated satisfactory image quality and excellent NPV for hemodynamically significant stenosis. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120859/-/DC1.

Gadofosveset trisodium: abdominal and peripheral vascular applications.

OBJECTIVE: The purpose of this review is to illustrate various applications of gadofosveset trisodium in evaluating abdominal and peripheral vascular disease. The basic properties, technical considerations, and clinical and potential future applications of gadofosveset are described. CONCLUSION: Gadofosveset trisodium facilitates comprehensive high-resolution arterial and venous MR angiography. Because of its prolonged intravascular residence time, gadofosveset trisodium is particularly useful for evaluating venous, dynamic, and functional vascular disease with a single low-dose contrast injection.

The development of the pediatric stroke neuroimaging platform (PEDSNIP).

Childhood stroke occurs from birth to 18 years of age, ranks among the top ten childhood causes of death, and leaves lifelong neurological impairments. Arterial ischemic stroke in infancy and childhood occurs due to arterial occlusion in the brain, resulting in a focal lesion. Our understanding of mechanisms of injury and repair associated with focal injury in the developing brain remains rudimentary. Neuroimaging can reveal important insights into these mechanisms. In adult stroke population, multi-center neuroimaging studies are common and have accelerated the translation process leading to improvements in treatment and outcome. These studies are centered on the growing evidence that neuroimaging measures and other biomarkers (e.g., from blood and cerebrospinal fluid) can enhance our understanding of mechanisms of risk and injury and be used as complementary outcome markers. These factors have yet to be studied in pediatric stroke because most neuroimaging studies in this population have been conducted in single-centred, small cohorts. By pooling neuroimaging data across multiple sites, larger cohorts of patients can significantly boost study feasibility and power in elucidating mechanisms of brain injury, repair and outcomes. These aims are particularly relevant in pediatric stroke because of the decreased incidence rates and the lack of mechanism-targeted trials. Toward these aims, we developed the Pediatric Stroke Neuroimaging Platform (PEDSNIP) in 2015, funded by The Brain Canada Platform Support Grant, to focus on three identified neuroimaging priorities. These were: developing and harmonizing multisite clinical protocols, creating the infrastructure and methods to import, store and organize the large clinical neuroimaging dataset from multiple sites through the International Pediatric Stroke Study (IPSS), and enabling central searchability. To do this, developed a two-pronged approach that included building 1) A Clinical-MRI Data Repository (standard of care imaging) linked to clinical data and longitudinal outcomes and 2) A Research-MRI neuroimaging data set acquired through our extensive collaborative, multi-center, multidisciplinary network. This dataset was collected prospectively in eight North American centers to test the feasibility and implementation of harmonized advanced Research-MRI, with the addition of clinical information, genetic and proteomic studies, in a cohort of children presenting with acute ischemic stroke. Here we describe the process that enabled the development of PEDSNIP built to provide the infrastructure to support neuroimaging research priorities in pediatric stroke. Having built this Platform, we are now able to utilize the largest neuroimaging and clinical data pool on pediatric stroke data worldwide to conduct hypothesis-driven research. We are actively working on a bioinformatics approach to develop predictive models of risk, injury and repair and accelerate breakthrough discoveries leading to mechanism-targeted treatments that improve outcomes and minimize the burden following childhood stroke. This unique transformational resource for scientists and researchers has the potential to result in a paradigm shift in the management, outcomes and quality of life in children with stroke and their families, with far-reaching benefits for other brain conditions of people across the lifespan.

Intraobserver and interobserver variability of renal volume measurements in polycystic kidney disease using a semiautomated MR segmentation algorithm.

OBJECTIVE: Total renal volume and changes in kidney volume are markers of disease progression in autosomal-dominant polycystic kidney disease (ADPKD) but are not used in clinical practice in part because of the complexity of manual measurements. This study aims to assess the intra- and interobserver reproducibility of a semiautomated renal volumetric algorithm using fluid-sensitive MRI pulse sequences. SUBJECTS AND METHODS: Renal volumes of 17 patients with ADPKD were segmented from high-resolution coronal HASTE and true fast imaging with steady-state precession (FISP) MR acquisitions. Measurements performed independently by four readers were repeated, typically after 7 days. Intraobserver agreement indexes were calculated for total kidney volume for each patient. Interobserver agreement indexes were obtained for the six paired combinations of readers as well as for two readers after rigorous formalized training. Pearson and concordance correlation coefficients, coefficients of variation (CVs), and 95% limits of agreement were determined. RESULTS: The HASTE and true FISP sequences performed similarly with a median intraobserver agreement of greater than 98.1% and a CV of less than 2.4% across all readers. The median interobserver agreement was greater than 95.2% and the CV was less than 7.1%, across all reader pairs. Reader training further lowered interobserver CV. The mean total kidney volume was 1420 mL (range, 331-3782 mL) for HASTE imaging and 1445 mL (range, 301-3714 mL) for true FISP imaging, with mean image processing times per patient of 43 and 28 minutes, respectively. CONCLUSION: This semiautomated MR volumetric algorithm provided excellent intraobserver and very good interobserver reproducibility using fluid-sensitive pulse sequences that emphasize cyst conspicuity.