Health system-scale language models are all-purpose prediction engines.

Physicians make critical time-constrained decisions every day. Clinical predictive models can help physicians and administrators make decisions by forecasting clinical and operational events. Existing structured data-based clinical predictive models have limited use in everyday practice owing to complexity in data processing, as well as model development and deployment1-3. Here we show that unstructured clinical notes from the electronic health record can enable the training of clinical language models, which can be used as all-purpose clinical predictive engines with low-resistance development and deployment. Our approach leverages recent advances in natural language processing4,5 to train a large language model for medical language (NYUTron) and subsequently fine-tune it across a wide range of clinical and operational predictive tasks. We evaluated our approach within our health system for five such tasks: 30-day all-cause readmission prediction, in-hospital mortality prediction, comorbidity index prediction, length of stay prediction, and insurance denial prediction. We show that NYUTron has an area under the curve (AUC) of 78.7-94.9%, with an improvement of 5.36-14.7% in the AUC compared with traditional models. We additionally demonstrate the benefits of pretraining with clinical text, the potential for increasing generalizability to different sites through fine-tuning and the full deployment of our system in a prospective, single-arm trial. These results show the potential for using clinical language models in medicine to read alongside physicians and provide guidance at the point of care.

Variable generalization performance of a deep learning model to detect pneumonia in chest radiographs: A cross-sectional study.

BACKGROUND: There is interest in using convolutional neural networks (CNNs) to analyze medical imaging to provide computer-aided diagnosis (CAD). Recent work has suggested that image classification CNNs may not generalize to new data as well as previously believed. We assessed how well CNNs generalized across three hospital systems for a simulated pneumonia screening task. METHODS AND FINDINGS: A cross-sectional design with multiple model training cohorts was used to evaluate model generalizability to external sites using split-sample validation. A total of 158,323 chest radiographs were drawn from three institutions: National Institutes of Health Clinical Center (NIH; 112,120 from 30,805 patients), Mount Sinai Hospital (MSH; 42,396 from 12,904 patients), and Indiana University Network for Patient Care (IU; 3,807 from 3,683 patients). These patient populations had an age mean (SD) of 46.9 years (16.6), 63.2 years (16.5), and 49.6 years (17) with a female percentage of 43.5%, 44.8%, and 57.3%, respectively. We assessed individual models using the area under the receiver operating characteristic curve (AUC) for radiographic findings consistent with pneumonia and compared performance on different test sets with DeLong's test. The prevalence of pneumonia was high enough at MSH (34.2%) relative to NIH and IU (1.2% and 1.0%) that merely sorting by hospital system achieved an AUC of 0.861 (95% CI 0.855-0.866) on the joint MSH-NIH dataset. Models trained on data from either NIH or MSH had equivalent performance on IU (P values 0.580 and 0.273, respectively) and inferior performance on data from each other relative to an internal test set (i.e., new data from within the hospital system used for training data; P values both <0.001). The highest internal performance was achieved by combining training and test data from MSH and NIH (AUC 0.931, 95% CI 0.927-0.936), but this model demonstrated significantly lower external performance at IU (AUC 0.815, 95% CI 0.745-0.885, P = 0.001). To test the effect of pooling data from sites with disparate pneumonia prevalence, we used stratified subsampling to generate MSH-NIH cohorts that only differed in disease prevalence between training data sites. When both training data sites had the same pneumonia prevalence, the model performed consistently on external IU data (P = 0.88). When a 10-fold difference in pneumonia rate was introduced between sites, internal test performance improved compared to the balanced model (10× MSH risk P < 0.001; 10× NIH P = 0.002), but this outperformance failed to generalize to IU (MSH 10× P < 0.001; NIH 10× P = 0.027). CNNs were able to directly detect hospital system of a radiograph for 99.95% NIH (22,050/22,062) and 99.98% MSH (8,386/8,388) radiographs. The primary limitation of our approach and the available public data is that we cannot fully assess what other factors might be contributing to hospital system-specific biases. CONCLUSION: Pneumonia-screening CNNs achieved better internal than external performance in 3 out of 5 natural comparisons. When models were trained on pooled data from sites with different pneumonia prevalence, they performed better on new pooled data from these sites but not on external data. CNNs robustly identified hospital system and department within a hospital, which can have large differences in disease burden and may confound predictions.

Relationship between dynamical entropy and energy dissipation far from thermodynamic equilibrium.

Connections between microscopic dynamical observables and macroscopic nonequilibrium (NE) properties have been pursued in statistical physics since Boltzmann, Gibbs, and Maxwell. The simulations we describe here establish a relationship between the Kolmogorov-Sinai entropy and the energy dissipated as heat from a NE system to its environment. First, we show that the Kolmogorov-Sinai or dynamical entropy can be separated into system and bath components and that the entropy of the system characterizes the dynamics of energy dissipation. Second, we find that the average change in the system dynamical entropy is linearly related to the average change in the energy dissipated to the bath. The constant energy and time scales of the bath fix the dynamical relationship between these two quantities. These results provide a link between microscopic dynamical variables and the macroscopic energetics of NE processes.

Generative large language models are all-purpose text analytics engines: text-to-text learning is all your need.

OBJECTIVE: To solve major clinical natural language processing (NLP) tasks using a unified text-to-text learning architecture based on a generative large language model (LLM) via prompt tuning. METHODS: We formulated 7 key clinical NLP tasks as text-to-text learning and solved them using one unified generative clinical LLM, GatorTronGPT, developed using GPT-3 architecture and trained with up to 20 billion parameters. We adopted soft prompts (ie, trainable vectors) with frozen LLM, where the LLM parameters were not updated (ie, frozen) and only the vectors of soft prompts were updated, known as prompt tuning. We added additional soft prompts as a prefix to the input layer, which were optimized during the prompt tuning. We evaluated the proposed method using 7 clinical NLP tasks and compared them with previous task-specific solutions based on Transformer models. RESULTS AND CONCLUSION: The proposed approach achieved state-of-the-art performance for 5 out of 7 major clinical NLP tasks using one unified generative LLM. Our approach outperformed previous task-specific transformer models by ∼3% for concept extraction and 7% for relation extraction applied to social determinants of health, 3.4% for clinical concept normalization, 3.4%-10% for clinical abbreviation disambiguation, and 5.5%-9% for natural language inference. Our approach also outperformed a previously developed prompt-based machine reading comprehension (MRC) model, GatorTron-MRC, for clinical concept and relation extraction. The proposed approach can deliver the "one model for all" promise from training to deployment using a unified generative LLM.

A study of generative large language model for medical research and healthcare.

There are enormous enthusiasm and concerns in applying large language models (LLMs) to healthcare. Yet current assumptions are based on general-purpose LLMs such as ChatGPT, which are not developed for medical use. This study develops a generative clinical LLM, GatorTronGPT, using 277 billion words of text including (1) 82 billion words of clinical text from 126 clinical departments and approximately 2 million patients at the University of Florida Health and (2) 195 billion words of diverse general English text. We train GatorTronGPT using a GPT-3 architecture with up to 20 billion parameters and evaluate its utility for biomedical natural language processing (NLP) and healthcare text generation. GatorTronGPT improves biomedical natural language processing. We apply GatorTronGPT to generate 20 billion words of synthetic text. Synthetic NLP models trained using synthetic text generated by GatorTronGPT outperform models trained using real-world clinical text. Physicians' Turing test using 1 (worst) to 9 (best) scale shows that there are no significant differences in linguistic readability (p = 0.22; 6.57 of GatorTronGPT compared with 6.93 of human) and clinical relevance (p = 0.91; 7.0 of GatorTronGPT compared with 6.97 of human) and that physicians cannot differentiate them (p < 0.001). This study provides insights into the opportunities and challenges of LLMs for medical research and healthcare.

Population scale latent space cohort matching for the improved use and exploration of observational trial data.

A significant amount of clinical research is observational by nature and derived from medical records, clinical trials, and large-scale registries. While there is no substitute for randomized, controlled experimentation, such experiments or trials are often costly, time consuming, and even ethically or practically impossible to execute. Combining classical regression and structural equation modeling with matching techniques can leverage the value of observational data. Nevertheless, identifying variables of greatest interest in high-dimensional data is frequently challenging, even with application of classical dimensionality reduction and/or propensity scoring techniques. Here, we demonstrate that projecting high-dimensional medical data onto a lower-dimensional manifold using deep autoencoders and post-hoc generation of treatment/control cohorts based on proximity in the lower-dimensional space results in better matching of confounding variables compared to classical propensity score matching (PSM) in the original high-dimensional space (P<0.0001) and performs similarly to PSM models constructed by experts with prior knowledge of the underlying pathology when evaluated on predicting risk ratios from real-world clinical data. Thus, in cases when the underlying problem is poorly understood and the data is high-dimensional in nature, matching in the autoencoder latent space might be of particular benefit.

Deploying deep learning models on unseen medical imaging using adversarial domain adaptation.

The fundamental challenge in machine learning is ensuring that trained models generalize well to unseen data. We developed a general technique for ameliorating the effect of dataset shift using generative adversarial networks (GANs) on a dataset of 149,298 handwritten digits and dataset of 868,549 chest radiographs obtained from four academic medical centers. Efficacy was assessed by comparing area under the curve (AUC) pre- and post-adaptation. On the digit recognition task, the baseline CNN achieved an average internal test AUC of 99.87% (95% CI, 99.87-99.87%), which decreased to an average external test AUC of 91.85% (95% CI, 91.82-91.88%), with an average salvage of 35% from baseline upon adaptation. On the lung pathology classification task, the baseline CNN achieved an average internal test AUC of 78.07% (95% CI, 77.97-78.17%) and an average external test AUC of 71.43% (95% CI, 71.32-71.60%), with a salvage of 25% from baseline upon adaptation. Adversarial domain adaptation leads to improved model performance on radiographic data derived from multiple out-of-sample healthcare populations. This work can be applied to other medical imaging domains to help shape the deployment toolkit of machine learning in medicine.

A large language model for electronic health records.

There is an increasing interest in developing artificial intelligence (AI) systems to process and interpret electronic health records (EHRs). Natural language processing (NLP) powered by pretrained language models is the key technology for medical AI systems utilizing clinical narratives. However, there are few clinical language models, the largest of which trained in the clinical domain is comparatively small at 110 million parameters (compared with billions of parameters in the general domain). It is not clear how large clinical language models with billions of parameters can help medical AI systems utilize unstructured EHRs. In this study, we develop from scratch a large clinical language model-GatorTron-using >90 billion words of text (including >82 billion words of de-identified clinical text) and systematically evaluate it on five clinical NLP tasks including clinical concept extraction, medical relation extraction, semantic textual similarity, natural language inference (NLI), and medical question answering (MQA). We examine how (1) scaling up the number of parameters and (2) scaling up the size of the training data could benefit these NLP tasks. GatorTron models scale up the clinical language model from 110 million to 8.9 billion parameters and improve five clinical NLP tasks (e.g., 9.6% and 9.5% improvement in accuracy for NLI and MQA), which can be applied to medical AI systems to improve healthcare delivery. The GatorTron models are publicly available at: https://catalog.ngc.nvidia.com/orgs/nvidia/teams/clara/models/gatortron_og .

Multivariate statistical identification of human bladder carcinomas using ambient ionization imaging mass spectrometry.

Diagnosis of human bladder cancer in untreated tissue sections is achieved by using imaging data from desorption electrospray ionization mass spectrometry (DESI-MS) combined with multivariate statistical analysis. We use the distinctive DESI-MS glycerophospholipid (GP) mass spectral profiles to visually characterize and formally classify twenty pairs (40 tissue samples) of human cancerous and adjacent normal bladder tissue samples. The individual ion images derived from the acquired profiles correlate with standard histological hematoxylin and eosin (H&E)-stained serial sections. The profiles allow us to classify the disease status of the tissue samples with high accuracy as judged by reference histological data. To achieve this, the data from the twenty pairs were divided into a training set and a validation set. Spectra from the tumor and normal regions of each of the tissue sections in the training set were used for orthogonal projection to latent structures (O-PLS) treated partial least-square discriminate analysis (PLS-DA). This predictive model was then validated by using the validation set and showed a 5% error rate for classification and a misclassification rate of 12%. It was also used to create synthetic images of the tissue sections showing pixel-by-pixel disease classification of the tissue and these data agreed well with the independent classification that uses histological data by a certified pathologist. This represents the first application of multivariate statistical methods for classification by ambient ionization although these methods have been applied previously to other MS imaging methods. The results are encouraging in terms of the development of a method that could be utilized in a clinical setting through visualization and diagnosis of intact tissue.

Direct detection of fatty acid ethyl esters using low temperature plasma (LTP) ambient ionization mass spectrometry for rapid bacterial differentiation.

Low temperature plasma mass spectrometry (LTP-MS) was employed to detect fatty acid ethyl esters (FAEE) from bacterial samples directly. Positive ion mode FAEE mass spectrometric profiles of sixteen different bacterial samples were obtained without extraction or other sample preparation. In the range m/z 200-300, LTP mass spectra show highly reproducible and characteristic patterns. To identify the FAEE's associated with the characteristic peaks, accurate masses were recorded in the full scan mode using an LTQ/Orbitrap instrument, and tandem mass spectrometry was performed. Data were examined by principal component analysis (PCA) to determine the degree of differentiation possible amongst different bacterial species. Gram-positive and gram-negative bacteria are readily distinguished, and 11 out of 13 Salmonella strains show distinctive patterns. Growth media effects are observed but do not interfere with species recognition based on the PCA results.

Data quality in tissue analysis using desorption electrospray ionization.

There has been a recent surge in applications of mass spectrometry (MS) to tissue analysis, particularly lipid-based tissue imaging using ambient ionization techniques. This recent growth highlights the need to examine the effects of sample handling, storage conditions, and experimental protocols on the quality of the data obtained. Variables such as time before freezing after organ removal, storage time at -80 °C, time stored at room temperature, heating, and freeze/thaw cycles were investigated for their effect on the data quality obtained in desorption electrospray ionization (DESI)-MS using mouse brain. In addition, analytical variables such as tissue thickness, drying times, and instrumental conditions were also examined for their impact on DESI-MS data. While no immediate changes were noted in the DESI-MS lipid profiles of the mouse brain tissue after spending 1 h at room temperature when compared to being frozen immediately following removal, minor changes were noted between the tissue samples after 7 months of storage at -80 °C. In tissue sections stored at room temperature, degradation was noted in 24 h by the appearance of fatty acid dimers, which are indicative of high fatty acid concentrations, while in contrast, those sections stored at -80 °C for 7 months showed no significant degradation. Tissue sections were also subjected to up to six freeze/thaw cycles and showed increasing degradation following each cycle. In addition, tissue pieces were subjected to 50 °C temperatures and analyzed at specific time points. In as little as 2 h, degradation was observed in the form of increased fatty acid dimer formation, indicating that enzymatic processes forming free fatty acids were still active in the tissue. We have associated these dimers with high concentrations of free fatty acids present in the tissue during DESI-MS experiments. Analytical variables such as tissue thickness and time left to dry under nitrogen were also investigated, with no change in the resulting profiles at thickness from 10 to 25 µm and with optimal signal obtained after just 20 min in the dessicator. Experimental conditions such as source parameters, spray solvents, and sample surfaces are all shown to impact the quality of the data. Inter-section (relative standard deviation (%RSD), 0.44-7.2%) and intra-sample (%RSD, 4.0-8.0%) reproducibility data show the high quality information DESI-MS provides. Overall, the many variables investigated here showed DESI-MS to be a robust technique, with sample storage conditions having the most effect on the data obtained, and with unacceptable sample degradation occurring during room temperature storage.

Origin of chiral selectivity in gas-phase serine tetramers.

Serine "magic-number" clusters have attracted substantial experimental and theoretical interest since their discovery. Serine undergoes marked chiral enrichment upon sublimation, which has been associated with the homochiral selectivity of the octamer. This process has been implicated in one possible mechanism leading to the origin of biological homochirality. While the octamer is the best known of the serine clusters, here we focus on the tetramer, the smallest serine cluster known to exhibit homochiral preference. This choice is based on its greater simplicity and tractability with accessible computational resources. Basin-hopping molecular dynamics simulations coupled to density functional theory calculations yield a "structural landscape" for low-lying configurations on the potential energy surface. The full range of enantiomeric compositions and charge states is investigated. Global energy minimum serine tetramers consist of a cage structure bonded by zwitterionic terminal groups. The participation of the serine hydroxyl side chains in hydrogen bonds with adjacent monomers drives the homochiral selectivity of serine tetramers. The configuration of the hydrogen bonding network is strongly dependent on enantiomeric composition and charge state. Smaller cations are incorporated into the center of the tetramer cage and effectively disable all side chain hydrogen bonding, while larger cations appear not to incorporate into the tetramer cage and are stabilized outside only in the homochiral case. The current theoretical data requires the introduction of a kinetic barrier to complete the model, limiting rearrangement from the basic cage configuration in some cases, which is discussed and probed directly by doubly-nudged elastic band transition state searches. These calculations elucidate a large barrier for reorganization of the cage, completing the theoretical understanding of the tetramers.

Deep anomaly detection of seizures with paired stereoelectroencephalography and video recordings.

Real-time seizure detection is a resource intensive process as it requires continuous monitoring of patients on stereoelectroencephalography. This study improves real-time seizure detection in drug resistant epilepsy (DRE) patients by developing patient-specific deep learning models that utilize a novel self-supervised dynamic thresholding approach. Deep neural networks were constructed on over 2000 h of high-resolution, multichannel SEEG and video recordings from 14 DRE patients. Consensus labels from a panel of epileptologists were used to evaluate model efficacy. Self-supervised dynamic thresholding exhibited improvements in positive predictive value (PPV; difference: 39.0%; 95% CI 4.5-73.5%; Wilcoxon-Mann-Whitney test; N = 14; p = 0.03) with similar sensitivity (difference: 14.3%; 95% CI - 21.7 to 50.3%; Wilcoxon-Mann-Whitney test; N = 14; p = 0.42) compared to static thresholds. In some models, training on as little as 10 min of SEEG data yielded robust detection. Cross-testing experiments reduced PPV (difference: 56.5%; 95% CI 25.8-87.3%; Wilcoxon-Mann-Whitney test; N = 14; p = 0.002), while multimodal detection significantly improved sensitivity (difference: 25.0%; 95% CI 0.2-49.9%; Wilcoxon-Mann-Whitney test; N = 14; p < 0.05). Self-supervised dynamic thresholding improved the efficacy of real-time seizure predictions. Multimodal models demonstrated potential to improve detection. These findings are promising for future deployment in epilepsy monitoring units to enable real-time seizure detection without annotated data and only minimal training time in individual patients.

Predicting adult neuroscience intensive care unit admission from emergency department triage using a retrospective, tabular-free text machine learning approach.

Early admission to the neurosciences intensive care unit (NSICU) is associated with improved patient outcomes. Natural language processing offers new possibilities for mining free text in electronic health record data. We sought to develop a machine learning model using both tabular and free text data to identify patients requiring NSICU admission shortly after arrival to the emergency department (ED). We conducted a single-center, retrospective cohort study of adult patients at the Mount Sinai Hospital, an academic medical center in New York City. All patients presenting to our institutional ED between January 2014 and December 2018 were included. Structured (tabular) demographic, clinical, bed movement record data, and free text data from triage notes were extracted from our institutional data warehouse. A machine learning model was trained to predict likelihood of NSICU admission at 30 min from arrival to the ED. We identified 412,858 patients presenting to the ED over the study period, of whom 1900 (0.5%) were admitted to the NSICU. The daily median number of ED presentations was 231 (IQR 200-256) and the median time from ED presentation to the decision for NSICU admission was 169 min (IQR 80-324). A model trained only with text data had an area under the receiver-operating curve (AUC) of 0.90 (95% confidence interval (CI) 0.87-0.91). A structured data-only model had an AUC of 0.92 (95% CI 0.91-0.94). A combined model trained on structured and text data had an AUC of 0.93 (95% CI 0.92-0.95). At a false positive rate of 1:100 (99% specificity), the combined model was 58% sensitive for identifying NSICU admission. A machine learning model using structured and free text data can predict NSICU admission soon after ED arrival. This may potentially improve ED and NSICU resource allocation. Further studies should validate our findings.

Combining Initial Radiographs and Clinical Variables Improves Deep Learning Prognostication in Patients with COVID-19 from the Emergency Department.

PURPOSE: To train a deep learning classification algorithm to predict chest radiograph severity scores and clinical outcomes in patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In this retrospective cohort study, patients aged 21-50 years who presented to the emergency department (ED) of a multicenter urban health system from March 10 to 26, 2020, with COVID-19 confirmation at real-time reverse-transcription polymerase chain reaction screening were identified. The initial chest radiographs, clinical variables, and outcomes, including admission, intubation, and survival, were collected within 30 days (n = 338; median age, 39 years; 210 men). Two fellowship-trained cardiothoracic radiologists examined chest radiographs for opacities and assigned a clinically validated severity score. A deep learning algorithm was trained to predict outcomes on a holdout test set composed of patients with confirmed COVID-19 who presented between March 27 and 29, 2020 (n = 161; median age, 60 years; 98 men) for both younger (age range, 21-50 years; n = 51) and older (age >50 years, n = 110) populations. Bootstrapping was used to compute CIs. RESULTS: The model trained on the chest radiograph severity score produced the following areas under the receiver operating characteristic curves (AUCs): 0.80 (95% CI: 0.73, 0.88) for the chest radiograph severity score, 0.76 (95% CI: 0.68, 0.84) for admission, 0.66 (95% CI: 0.56, 0.75) for intubation, and 0.59 (95% CI: 0.49, 0.69) for death. The model trained on clinical variables produced an AUC of 0.64 (95% CI: 0.55, 0.73) for intubation and an AUC of 0.59 (95% CI: 0.50, 0.68) for death. Combining chest radiography and clinical variables increased the AUC of intubation and death to 0.88 (95% CI: 0.79, 0.96) and 0.82 (95% CI: 0.72, 0.91), respectively. CONCLUSION: The combination of imaging and clinical information improves outcome predictions.Supplemental material is available for this article.© RSNA, 2020.

Cholesterol sulfate imaging in human prostate cancer tissue by desorption electrospray ionization mass spectrometry.

Development of methods for rapid distinction between cancerous and non-neoplastic tissues is an important goal in disease diagnosis. To this end, desorption electrospray ionization mass spectrometry (DESI-MS) imaging was applied to analyze the lipid profiles of thin tissue sections of 68 samples of human prostate cancer and normal tissue. The disease state of the tissue sections was determined by independent histopathological examination. Cholesterol sulfate was identified as a differentiating compound, found almost exclusively in cancerous tissues including tissue containing precancerous lesions. The presence of cholesterol sulfate in prostate tissues might serve as a tool for prostate cancer diagnosis although confirmation through larger and more diverse cohorts and correlations with clinical outcome data is needed.

Multivariate statistical differentiation of renal cell carcinomas based on lipidomic analysis by ambient ionization imaging mass spectrometry.

Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of 11 sample pairs of human papillary renal cell carcinoma (RCC) and adjacent normal tissue and nine sample pairs of clear cell RCC and adjacent normal tissue. DESI-MS images showing the spatial distributions of particular glycerophospholipids (GPs) and free fatty acids in the negative ion mode were compared to serial tissue sections stained with hematoxylin and eosin (H&E). Increased absolute intensities as well as changes in relative abundance were seen for particular compounds in the tumor regions of the samples. Multivariate statistical analysis using orthogonal projection to latent structures treated partial least square discriminate analysis (PLS-DA) was used for visualization and classification of the tissue pairs using the full mass spectra as predictors. PLS-DA successfully distinguished tumor from normal tissue for both papillary and clear cell RCC with misclassification rates obtained from the validation set of 14.3% and 7.8%, respectively. It was also used to distinguish papillary and clear cell RCC from each other and from the combined normal tissues with a reasonable misclassification rate of 23%, as determined from the validation set. Overall DESI-MS imaging combined with multivariate statistical analysis shows promise as a molecular pathology technique for diagnosing cancerous and normal tissue on the basis of GP profiles.

Differential Subsampling with Cartesian Ordering for Ultrafast High-Resolution MRA in the Assessment of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: We aimed to evaluate the feasibility of an ultrafast whole head contrast-enhanced MRA (CE-MRA) in morphometric assessment of intracranial aneurysms in comparison to routinely used time-of-flight (TOF)-MRA. METHODS: In this prospective single institutional study, patients with known untreated intracranial aneurysm underwent MRA. Routine multislab TOF-MRA was obtained with a 3D voxel sizes of .6 × .6 × 1 (6-minute acquisition time). CE-MRA of whole head was obtained using Differential Subsampling with Cartesian Ordering (DISCO) and 2D Auto-calibrating Reconstruction for Cartesian imaging with a 3D voxel-sizes of .75 × .75 × 1 mm3 during a 6-second temporal resolution. Morphometric features of intracranial aneurysms, including size, aneurysm sac morphology, and the presence of intraluminal thrombosis, were assessed on both techniques. Statistical analysis was performed using a combination of Kappa test, Bland-Altman, and correlation coefficient analysis. RESULTS: A total of 34 aneurysms in 28 patients were included. Aneurysm size measurements (mean ± SD) were similar between DISCO-MRA (4.1 ± 2.3 mm) and TOF-MRA (4.3 ± 2.8 mm) (P = .27). Bland-Altman analysis showed a mean difference of .4 mm and there was excellent correlation r = .91 (95% CI: .87-.96). In six aneurysms (17.6%), TOF-MRA was nonconfidant to exclude intraluminal thrombosis. In seven aneurysms (20%), TOF-MRA was unable or nonconfidant in depicting aneurysm sac morphology. CONCLUSIONS: Described ultrafast high spatial-resolution MRA is superior to routinely used TOF-MRA in assessment of morphometric features of intracranial aneurysms, such as intraluminal thrombosis and aneurysm morphology, and is obtained in a fraction of the time (6 seconds).

A technical comparison of thrombectomy vacuum aspiration systems.

INTRODUCTION: Improved functional outcomes after mechanical thrombectomy for emergent large vessel occlusion depend on expedient reperfusion after clinical presentation. Device technology has improved substantially over the years, and several commercial options exist for both large-bore aspiration catheters and suction pump systems. OBJECTIVE: To compare various vacuum pumps and examine the aspiration forces they generate as well as the force of catheter tip detachment from an artificial thrombus. METHODS: Using an artificial thrombus made from polyvinyl alcohol gel, we tested various mechanical characteristics of commercially available suction pumps, including the Penumbra Jet Engine, Penumbra Max, Stryker Medela AXS, Microvention Gomco, and a 60 cc syringe. Both aspiration pressure and tip force generated were analyzed. Subsequently, a cohort of thrombectomy catheters were assessed using the Penumbra Jet Engine to determine tip forces generated on an artificial thrombus. One-way analysis of variance was used to assess statistical significance. RESULTS: The Penumbra Jet Engine system generated both the highest maximum aspiration pressures (28.8 inches Hg) and the highest tip force (23.68 grams force (gf)) on an artificial thrombus, with statistical significance compared with the other pump systems. Using the Jet Engine, the largest-bore catheter was associated with the highest tip force (32.12 gf). The overall correlation coefficient between catheter inner diameter and tip force was 0.98. CONCLUSIONS: The Penumbra Jet Engine pump generates significantly higher vacuum pressures and tip forces than the other commercially available aspiration pump systems. Furthermore, catheters with a larger inner diameter generate higher tip suction forces on aspiration. Whether these mechanical features lead to improved clinical outcomes is yet to be determined.

Lipid profiles of canine invasive transitional cell carcinoma of the urinary bladder and adjacent normal tissue by desorption electrospray ionization imaging mass spectrometry.

Desorption electrospray ionization mass spectrometry (DESI-MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids, and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis was also used to generate unsupervised statistical images from the negative ion mode data, and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E-stained tissue.