Comparison of image quality and diagnostic efficacy of routine clinical lumbar spine imaging at 0.55T and 1.5/3T.

PURPOSE: To compare image quality, assess inter-reader variability, and evaluate the diagnostic efficacy of routine clinical lumbar spine sequences at 0.55T compared with those collected at 1.5/3T to assess common spine pathology. METHODS: 665 image series across 70 studies, collected at 0.55T and 1.5/3T, were assessed by two neuroradiology fellows for overall imaging quality (OIQ), artifacts, and accurate visualization of anatomical features (intervertebral discs, neural foramina, spinal cord, bone marrow, and conus / cauda equina nerve roots) using a 4-point Likert scale (1 = non-diagnostic to 4 = excellent). For the 0.55T scans, the most appropriate diagnosis(es) from a picklist of common spine pathologies was selected. The mean ± SD of all scores for all features for each sequence and reader at 0.55T and 1.5/3T were calculated. Paired t-tests (p ≤ 0.05) were used to compare ratings between field strengths. The inter-reader agreement was calculated using linear-weighted Cohen's Kappa coefficient (p ≤ 0.05). Unpaired VCG analysis for OIQ was additionally employed to represent differences between 0.55T and 1.5/3T (95 % CI). RESULTS: All sequences at 0.55T were rated as acceptable (≥2) for diagnostic use by both readers despite significantly lower scores for some compared to those at 1.5/3T. While there was low inter-reader agreement on individual scores, the agreement on the diagnosis was high, demonstrating the potential of this system for detecting routine spine pathology. CONCLUSIONS: Clinical lumbar spine imaging at 0.55T produces diagnostic-quality images demonstrating the feasibility of its use in diagnosing spinal pathology, including osteomyelitis/discitis, post-surgical changes with complications, and metastatic disease.

Direct Quantification of Gadolinium Retention in Young Patients by ICP-MS Analysis of Extracted Teeth.

In this 10-patient prospective pilot study, we show feasibility of pragmatic, direct ex vivo measurement of gadolinium retention from group II gadolinium-based contrast agents (GBCAs) in young patients following routine tooth extraction. This noninvasive method may support future research attempting to understand the link between GBCA exposure and clinical outcomes.

Abdominal MRI on a Commercial 0.55T System: Initial Evaluation and Comparison to Higher Field Strengths.

RATIONALE AND OBJECTIVES: This study aims to assess the quality of abdominal MR images acquired on a commercial 0.55T scanner and compare these images with those acquired on conventional 1.5T/3T scanners in both healthy subjects and patients. MATERIALS AND METHODS: Fifteen healthy subjects and 52 patients underwent abdominal Magnetic Resonance Imaging at 0.55T. Images were also collected in healthy subjects at 1.5T, and comparison 1.5/3T images identified for 28 of the 52 patients. Image quality was rated by two radiologists on a 4-point Likert scale. Readers were asked whether they could answer the clinical question for patient studies. Wilcoxon signed-rank test was used to test for significant differences in image ratings and acquisition times, and inter-reader reliability was computed. RESULTS: The overall image quality of all sequences at 0.55T were rated as acceptable in healthy subjects. Sequences were modified to improve signal-to-noise ratio and reduce artifacts and deployed for clinical use; 52 patients were enrolled in this study. Radiologists were able to answer the clinical question in 52 (reader 1) and 46 (reader 2) of the patient cases. Average image quality was considered to be diagnostic (>3) for all sequences except arterial phase FS 3D T1w gradient echo (GRE) and 3D magnetic resonance cholangiopancreatography for one reader. In comparison to higher field images, significantly lower scores were given to 0.55T IP 2D GRE and arterial phase FS 3D T1w GRE, and significantly higher scores to diffusion-weighted echo planar imaging at 0.55T; other sequences were equivalent. The average scan time at 0.55T was 54 ± 10 minutes vs 36 ± 11 minutes at higher field strengths (P < .001). CONCLUSION: Diagnostic-quality abdominal MR images can be obtained on a commercial 0.55T scanner at a longer overall acquisition time compared to higher field systems, although some sequences may benefit from additional optimization.

Gold nanoshells for prostate cancer treatment: evidence for deposition in abdominal organs.

PURPOSE: Gold-silica nanoshell therapy [AuroShells with subsequent focal laser therapy (AuroLase)] is an emerging targeted treatment modality for prostate cancer. We reviewed pre- and post-treatment unenhanced CT imaging to assess for retained gold-silica nanoshells in the abdomen and pelvis. METHODS: This single-institution retrospective study identified patients in the AuroLase pilot who underwent pre- and post-treatment unenhanced abdominopelvic CT. The attenuation, before and after gold-silica nanoshell administration, of the liver, spleen, pancreas, kidneys, prostate, blood pool, paraspinal musculature, and abnormal lymph nodes were manually measured by two readers. After inter-reader agreement was calculated using intraclass correlation (ICC), a permutation test was used to assess pre- and post-therapy attenuation differences. RESULTS: Four patients met the inclusion criteria. Mean age was 72.3 ± 5.9 years. Median time interval between pre-treatment CT and treatment, and between treatment and post-treatment CT, was 232 days and 236.5 days, respectively. The two readers' attenuation measurements had very high agreement (ICC = 0.99, p < 0.001). The highest differences in organ attenuation between pre- and post-therapy scans were seen in all four patients in the liver and spleen (liver increased by an average of 28.9 HU, p = 0.010; spleen increased by an average of 63.7 HU, p = 0.012). A single measured lymph node increased by an average of 58.9 HU. In the remainder of the measured sites, the change in attenuation from pre- to post-therapy scans ranged from -0.1 to 3.8 HU (p > 0.05). CONCLUSION: Increased attenuation of liver and spleen at CT can be an expected finding in patients who have received gold-silica nanoshell therapy.

Clinical Outcomes after Median Arcuate Ligament Release in Patients Responsive to Celiac Plexus Block.

PURPOSE: To determine if symptom relief with celiac plexus block (CPB) is associated with favorable clinical outcomes after median arcuate ligament release (MALR) surgery. MATERIALS AND METHODS: A retrospective review was performed from January 2000 to December 2021. Fifty-seven patients (42 women, 15 men; mean age, 43 years [range, 18-84 years]) with clinical and radiographic features suggestive of median arcuate ligament syndrome (MALS) underwent computed tomography (CT)-guided percutaneous CPB for suspected MALS. Clinical outcomes of CPB and MALR surgery were correlated. Adverse events were classified according to the Society of Interventional Radiology (SIR) guidelines. RESULTS: CT-guided percutaneous CPB was successfully performed in all 57 (100%) patients with suspected MALS. A cohort of 38 (67%) patients showed clinical improvement with CPB. A subset of 28 (74%) patients in this group subsequently underwent open MALR surgery; 27 (96%) responders to CPB showed favorable clinical outcomes with surgery. There was 1 (4%) CPB-related mild adverse event. There were no moderate, severe, or life-threatening adverse events. CONCLUSIONS: Patients who responded to CPB were selected to undergo surgery, and 96% of them improved after surgery.

Validation of the Minnesota Pectoralis Risk Score to predict mortality in the HeartMate 3 population.

BACKGROUND: The Minnesota Pectoralis Risk Score (MPRS) utilizes computed tomography-quantified thoracic muscle and clinical variables to predict survival after left ventricular assist device (LVAD) implantation. The model has not been prospectively tested in HeartMate 3 recipients. METHODS: A single-center HeartMate 3 cohort from July 2016 to July 2021 (n = 108) was utilized for this analysis. Cohort subjects with complete covariates for MPRS calculation (pectoralis muscle measures, Black race, creatinine, total bilirubin, body mass index, bridge to transplant status, and presence/absence of contrast) implanted after MPRS development were included. MPRS were calculated on each subject. Receiver operating characteristic curves were generated to test model discrimination at 30-day, 90-day, and 1-year mortality post-LVAD. Next, the performance of the 1-year post-LVAD outcome was compared to the HeartMate 3 survival risk score (HM3RS). RESULTS: The mean age was 58 (15 years), 80% (86/108) were male, and 26% (28/108) were destination therapy. The area under the curve (AUC) for the MPRS model to predict post-LVAD mortality was 0.73 at 30 days, 0.78 at 90 days, and 0.81 at 1 year. The AUC for the HM3RS for the 1-year outcome was 0.693. Each 1-unit point of the MPRS was associated with a significant increase in the hazard rate of death after LVAD (hazard ratio 2.1, 95% confidence interval 1.5-3.0, p < 0.0001). CONCLUSIONS: The MPRS had high performance in this prospective validation, particularly with respect to 90-day and 1-year post-LVAD mortality. Such a tool can provide additional information regarding risk stratification to aid informed decision-making.

DIMPLE: An R package to quantify, visualize, and model spatial cellular interactions from multiplex imaging with distance matrices.

A major challenge in the spatial analysis of multiplex imaging (MI) data is choosing how to measure cellular spatial interactions and how to relate them to patient outcomes. Existing methods to quantify cell-cell interactions do not scale to the rapidly evolving technical landscape, where both the number of unique cell types and the number of images in a dataset may be large. We propose a scalable analytical framework and accompanying R package, DIMPLE, to quantify, visualize, and model cell-cell interactions in the TME. By applying DIMPLE to publicly available MI data, we uncover statistically significant associations between image-level measures of cell-cell interactions and patient-level covariates.

Quality assessment of routine brain imaging at 0.55 T: initial experience in a clinical workflow.

The purpose of this study was to assess the quality of clinical brain imaging in healthy subjects and patients on an FDA-approved commercial 0.55 T MRI scanner, and to provide information about the feasibility of using this scanner in a clinical workflow. In this IRB-approved study, brain examinations on the scanner were prospectively performed in 10 healthy subjects (February-April 2022) and retrospectively derived from 44 patients (February-July 2022). Images collected using the following pulse sequences were available for assessment: axial DWI (diffusion-weighted imaging), apparent diffusion coefficient maps, 2D axial fluid-attenuated inversion recovery images, axial susceptibility-weighted images (both magnitude and phase), sagittal T1 -weighted (T1w) Sampling Perfection with Application Optimized Contrast images, sagittal T1w MPRAGE (magnetization prepared rapid gradient echo) with contrast enhancement, axial T1w turbo spin echo (TSE) with and without contrast enhancement, and axial T2 -weighted TSE. Two readers retrospectively and independently evaluated image quality and specific anatomical features in a blinded fashion on a four-point Likert scale, with a score of 1 being unacceptable and 4 being excellent, and determined the ability to answer the clinical question in patients. For each category of image sequences, the mean, standard deviation, and percentage of unacceptable quality images (<2) were calculated. Acceptable (rating ≥ 2) image quality was achieved at 0.55 T in all sequences for patients and 85% of the sequences for healthy subjects. Radiologists were able to answer the clinical question in all patients scanned. In total, 50% of the sequences used in patients and about 60% of the sequences used in healthy subjects exhibited good (rating ≥ 3) image quality. Based on these findings, we conclude that diagnostic quality clinical brain images can be successfully collected on this commercial 0.55 T scanner, indicating that the routine brain imaging protocol may be deployed on this system in the clinical workflow.

DIMPLE: AN R PACKAGE TO QUANTIFY, VISUALIZE, AND MODEL SPATIAL CELLULAR INTERACTIONS FROM MULTIPLEX IMAGING WITH DISTANCE MATRICES.

The tumor microenvironment (TME) is a complex ecosystem containing tumor cells, other surrounding cells, blood vessels, and extracellular matrix. Recent advances in multiplexed imaging technologies allow researchers to map several cellular markers in the TME at the single cell level while preserving their spatial locations. Evidence is mounting that cellular interactions in the TME can promote or inhibit tumor development and contribute to drug resistance. Current statistical approaches to quantify cell-cell interactions do not readily scale to the outputs of new imaging technologies which can distinguish many unique cell phenotypes in one image. We propose a scalable analytical framework and accompanying R package, DIMPLE, to quantify, visualize, and model cell-cell interactions in the TME. In application of DIMPLE to publicly available MI data, we uncover statistically significant associations between image-level measures of cell-cell interactions and patient-level covariates.

Association between calculated panel reactive antibody and waitlist outcomes in the 2018 heart allocation system.

BACKGROUND: The impact of heart transplant (HT) waitlist candidate sensitization on waitlist outcomes in the US is unknown. METHODS: Adult waitlist outcomes in OPTN (October 2018-September 2022) by calculated panel reactive antibody (cPRA) were modeled to identify thresholds of clinical significance. The primary outcome was the rate of HT by cPRA category (low: 0-35, middle: >35-90, high: >90) assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). The secondary outcome was waitlist removal for death or clinical deterioration. RESULTS: The elevated cPRA categories were associated with lower rates of HT. Candidates in the middle (35-90) and high cPRA categories (>90) had an adjusted 24% lower rate (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.80-0.92) and 61% lower rate (HR 0.39 95% CI. 0.33-0.47) of HT than the lowest category, respectively. Waitlist candidates in the high cPRA category listed in the top acuity strata (Statuses 1, 2) had increased rates of delisting for death or deterioration compared to those in the low cPRA category (adjusted HR 2.9, 95% CI 1.5-5.5), however, elevated cPRA (middle, high) was not associated with an increased rate of death and delisting when the cohort was considered as a whole. CONCLUSIONS: Elevated cPRA was associated with reduced rates of HT across all waitlist acuity tiers. Among HT waitlist candidates listed at the top acuity strata, the high cPRA category was associated with increased rates of delisting due to death or deterioration. Elevated cPRA may require consideration for critically ill candidates under continuous allocation.

Sex-Specific Outcomes of Candidates Listed as the Highest Priority Status for Heart Transplantation.

BACKGROUND: While sex differences in heart transplantation (HT) waitlist mortality have been previously described, waitlist and HT outcomes by sex of patients in the highest urgency strata (Status 1) since implementation of the 2018 allocation system change in the United States are unknown. We hypothesized that women listed as Status 1 may have worse outcomes due to adverse events on temporary mechanical circulatory support. METHODS: The analysis included adult, single-organ HT waitlist candidates listed as Status 1 at any time while listed, after the HT allocation system change (from October 18, 2018 through March 31, 2022). The primary outcome was the rate of HT by sex, assessed using multivariable competing risk analysis where waitlist removal for death or clinical deterioration was the competing event. Post-HT survival by sex of waitlist candidates transplanted as a Status 1 was also compared. RESULTS: Of 1120 Status 1 waitlist candidates (23.8% women), women had a lower rate of HT compared to men (adjusted hazard ratio, 0.74 [95% CI, 0.62-0.88]; P<0.001) and a higher rate of delisting for death or medical unsuitability (adjusted hazard ratio, 1.48 [95% CI, 1.05-2.09]; P=0.026). Calculated panel reactive antibody did not account for all the harm observed. Post-HT survival of Status 1 candidates by sex was similar (adjusted hazard ratio, 1.13 [95% CI, 0.62-2.06]; P=0.70). CONCLUSIONS: Women have a lower rate of HT and higher rate of delisting for death or clinical deterioration at the highest urgent status, which appears to be mediated but not fully explained by calculated panel reactive antibody levels. Further investigation into the safety profile of temporary mechanical circulatory support devices in women is needed.

Ultrasound appearance of regenerative peripheral nerve interface with clinical correlation.

OBJECTIVE: To describe the ultrasound (US) appearance of regenerative peripheral nerve interfaces (RPNIs) in humans, and correlate clinically and with histologic findings from rat RPNI. MATERIALS AND METHODS: Patients (≥ 18 years) who had undergone RPNI surgery within our institution between the dates of 3/2018 and 9/2019 were reviewed. A total of 21 patients (15 male, 6 female, age 21-82 years) with technically adequate US studies of RPNIs were reviewed. Clinical notes were reviewed for the presence of persistent pain after RPNI surgery. Histologic specimens of RPNIs in a rat model from prior studies were compared with the US findings noted in this study. RESULTS: There was a variable appearance to the RPNIs including focal changes involving the distal nerve, nerve-muscle graft junction, and area of the distal sutures. The muscle grafts varied in thickness with accompanying variable echogenic changes. No interval change was noted on follow-up US studies. Diffuse hypoechoic swelling with loss of the fascicular structure of the nerve within the RPNI and focal hypoechoic changes at the nerve-muscle graft junction were associated with clinical outcomes. US findings corresponded to histologic findings in the rat RPNI. CONCLUSION: Ultrasound imaging can demonstrate various morphologic changes involving the nerve, muscle, and interface between these two biological components of RPNIs. These changes correspond to expected degenerative and regenerative processes following nerve resection and muscle reinnervation and should not be misconstrued as pathologic in all cases. N5 and N1 morphologic type changes of the RPNI were found to be associated with symptoms.

A novel Bayesian functional spatial partitioning method with application to prostate cancer lesion detection using MRI.

Spatial partitioning methods correct for nonstationarity in spatially related data by partitioning the space into regions of local stationarity. Existing spatial partitioning methods can only estimate linear partitioning boundaries. This is inadequate for detecting an arbitrarily shaped anomalous spatial region within a larger area. We propose a novel Bayesian functional spatial partitioning (BFSP) algorithm, which estimates closed curves that act as partitioning boundaries around anomalous regions of data with a distinct distribution or spatial process. Our method utilizes transitions between a fixed Cartesian and moving polar coordinate system to model the smooth boundary curves using functional estimation tools. Using adaptive Metropolis-Hastings, the BFSP algorithm simultaneously estimates the partitioning boundary and the parameters of the spatial distributions within each region. Through simulation we show that our method is robust to shape of the target zone and region-specific spatial processes. We illustrate our method through the detection of prostate cancer lesions using magnetic resonance imaging.

Pre-operative sarcopenia is predictive of recurrent gastrointestinal bleeding on left ventricular assist device support: A multicenter analysis.

INTRODUCTION: Whether pre left ventricular assist device (LVAD) sarcopenia is associated with higher incidence of gastrointestinal bleeding (GIB) on LVAD support remains unknown. METHODS: To study the association between preoperative sarcopenia and post LVAD GIB events, we performed a retrospective, multi-centered study including patients with chest CTs performed ≤ 3 months prior to LVAD implantation at the University of Minnesota (n = 143) and Houston Methodist Hospital (n = 133). To quantify sarcopenia, unilateral pectoralis muscle mass indexed to body surface area (PMI) and attenuation (approximated by mean Hounsfield units; PHUm) were measured on pre-operative chest CT scans. Negative binomial regression analyses were performed to determine the association between pectoralis muscle measures and number of GIB events to 2 years of LVAD support. RESULTS: The study cohort included 276 LVAD recipients with 43 % designated as bridge to transplant at the time of LVAD implantation. High pectoralis muscle mass and tissue attenuation were both protective against GIB events. Each 5 unit increase in PHUm was associated with an adjusted 19 % reduction in the incidence rate of GIB (95 % CI 7-29 %, p = 0.002). Each unit increase in PMI was associated with an adjusted 17 % reduction in the incidence of GIB (95 % CI 1- 29 %, p = 0.04). The models were adjusted for age, sex, INTERMACS profile, bridge to transplant status, creatinine, albumin and implanting center. CONCLUSION: Preoperative sarcopenia, as quantified by pectoralis muscle size and attenuation, was associated with the development of recurrent GI bleeding after LVAD implantation. These CT quantitative measures appear to predict not only early mortality but morbidity on LVAD as well.

Assessment of U.S. heart transplantation equity as a function of race: Observational analyses of the OPTN database.

Background: Racial disparities in heart transplantation (HT) outcomes are suspected but uncertain. The additional impact of a recent change in donor allocation on disparities in HT in the United States (US) is unknown. We hypothesize racial disparities in HT are present and may be worsened by new allocation practices. Methods: Cohort: Adults listed for HT before and after a heart allocation policy change (Era 1: Oct 18th, 2015 - Oct 18th, 2018, Era 2: Oct 18th, 2018-June 30, 2021). The primary outcome was the rate of HT by race (Black vs. White), assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). Final adjusted models included co-morbidities, SES and community-level Social Determinants of Health. The secondary outcome was waitlist removal for death or clinical deterioration. Results: Of 17,384 waitlist candidates (Era 1: 9,150, Era 2: 8,234), Black waitlist candidates had a lower rate of HT compared to White waitlist candidates in Era 1 (adjusted HR 0·90, 95 % CI 0·84-0·97, p = 0·0053) and in Era 2 (adjusted HR 0·81, 95 % CI 0·75-0·88, p <0·0001, era race interaction p=0·056). The rate of waitlist removal for death or deterioration was similar between races in Era 1 (adjusted HR 0·92, 95 % 0·77-1·1, p = 0·38), but increased for Black candidates in Era 2 (adjusted HR 1·34, 95 % CI 1·09-1·65, p = 0·0054, era race interaction p = 0·0051). Interpretation: Both the measured rate of transplantation and rate of delisting for death or clinical deterioration have worsened for Black compared to White waitlist candidates under the new allocation system. Causes for these disparities require further study. Funding: University of Minnesota Department of Cardiology funds.

Heart Transplantation in Adriamycin-Associated Cardiomyopathy in the Contemporary Era of Advanced Heart Failure Therapies.

BACKGROUND: Adriamycin-associated cardiomyopathy (ACM) can lead to end-stage heart failure requiring advanced heart failure therapies. OBJECTIVES: This study sought to provide post-cardiac transplant survival data in patients with ACM in the contemporary era of mechanical circulatory support and cardiac transplantation. METHODS: Adults (≥18 years of age) who underwent first-time, single-organ heart transplantation were identified from the United Network for Organ Sharing between October 18, 2008, and October 18, 2018. Cardiomyopathy subtypes that could have been supported with a left ventricular assist device (LVAD) including ACM, dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM) were included. A multivariable Cox regression analysis was performed to determine the association between cardiomyopathy subtype and post-cardiac transplant survival. RESULTS: This analysis included 18,270 patients (357 with ACM; 10,662 with DCM; and 7,251 with ICM). Heart transplant recipients with ACM were younger, included more women, and had higher pulmonary vascular resistance at the time of listing. Patients with ACM had a lower percentage of durable LVADs at the time of transplant across all years of the study period. Patients with ACM did not experience an increase in post-cardiac transplant mortality compared to those with DCM (adjusted hazard ratio: 0.96; 95% confidence interval: 0.79 to 1.40; p = 0.764) or ICM (adjusted hazard ratio: 0.85; 95% confidence interval: 0.6 to 1.2; p = 0.304). CONCLUSIONS: Patients with ACM who received heart transplants between 2008 and 2018 had similar post-cardiac transplant survival to those with dilated and ischemic cardiomyopathy. Bridge-to-transplant LVAD use remains lower compared to other cardiomyopathy subtypes.

Heart Failure Severity Stratification Beyond INTERMACS Profiles: A Step Toward Optimal Left Ventricular Assist Device Timing.

The purpose of this analysis is to determine whether pectoralis muscle measures quantified on pre left ventricular assist device (LVAD) computerized tomography (CT) scans can identify subgroups of patients with differential disease severity within each Interagency Registry for Mechanical Circulatory Support (INTERMACS) profile. Patients with chest CTs performed ≤3 months before LVAD implantation at University of Minnesota (n = 143) and Houston Methodist Hospital (n = 133) were identified from the larger LVAD cohorts (University of Minnesota n = 353, Houston Methodist =278). Unilateral Pectoralis muscle mass indexed to body surface area and pectoralis muscle attenuation were measured on preoperative chest CT scans. Patients within each INTERMACS profile were separated into HIGH and LOW PEC muscle groups. Kaplan-Meier and multivariable cox regression analyses were performed to compare mortality among INTERMACS profiles by HIGH and LOW PEC muscle groups. INTERMACS 3 and 4 patients in the HIGH PEC groups had the highest survival on LVAD support (1 year survival 85% vs. 68%, log rank P = 0.0001). Being in this group was associated with a 60% reduction in the hazards rate (HR) of death after LVAD (adjusted HR 0.40, 95% confidence interval 0.25-0.62). Additionally, renal function deterioration in the year before LVAD was associated with lower INTERMACS profiles and lower measured pectoralis muscle tissue attenuation at the time of LVAD implantation. INTERMACS 3 and 4 patients with the highest pectoralis muscle measures had the best survival after LVAD. The association between renal function deterioration and sarcopenia suggests these muscle changes are progressive. Computerized tomography quantification of sarcopenia may help identify optimal LVAD implantation timing.

Pleiotropy informed adaptive association test of multiple traits using genome-wide association study summary data.

Genetic variants associated with disease outcomes can be used to develop personalized treatment. To reach this precision medicine goal, hundreds of large-scale genome-wide association studies (GWAS) have been conducted in the past decade to search for promising genetic variants associated with various traits. They have successfully identified tens of thousands of disease-related variants. However, in total these identified variants explain only part of the variation for most complex traits. There remain many genetic variants with small effect sizes to be discovered, which calls for the development of (a) GWAS with more samples and more comprehensively genotyped variants, for example, the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program is planning to conduct whole genome sequencing on over 100 000 individuals; and (b) novel and more powerful statistical analysis methods. The current dominating GWAS analysis approach is the "single trait" association test, despite the fact that many GWAS are conducted in deeply phenotyped cohorts including many correlated and well-characterized outcomes, which can help improve the power to detect novel variants if properly analyzed, as suggested by increasing evidence that pleiotropy, where a genetic variant affects multiple traits, is the norm in genome-phenome associations. We aim to develop pleiotropy informed powerful association test methods across multiple traits for GWAS. Since it is generally very hard to access individual-level GWAS phenotype and genotype data for those existing GWAS, due to privacy concerns and various logistical considerations, we develop rigorous statistical methods for pleiotropy informed adaptive multitrait association test methods that need only summary association statistics publicly available from most GWAS. We first develop a pleiotropy test, which has powerful performance for truly pleiotropic variants but is sensitive to the pleiotropy assumption. We then develop a pleiotropy informed adaptive test that has robust and powerful performance under various genetic models. We develop accurate and efficient numerical algorithms to compute the analytical P-value for the proposed adaptive test without the need of resampling or permutation. We illustrate the performance of proposed methods through application to joint association test of GWAS meta-analysis summary data for several glycemic traits. Our proposed adaptive test identified several novel loci missed by individual trait based GWAS meta-analysis. All the proposed methods are implemented in a publicly available R package.