Demystifying Large Language Models for Medicine: A Primer

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

Deep Learning Segmentation of Ascites on Abdominal CT Scans for Automatic Volume Quantification

Purpose: To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods: This retrospective study included contrast-enhanced and non-contrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years +/- 11 [s.d.]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results: On NIH-LC (25 patients; mean age, 59 years +/- 14 [s.d.]; 14 male) and NIH-OV (166 patients; mean age, 65 years +/- 9 [s.d.]; all female), the model achieved Dice scores of 0.855 +/- 0.061 (CI: 0.831-0.878) and 0.826 +/- 0.153 (CI: 0.764-0.887), with median volume estimation errors of 19.6% (IQR: 13.2-29.0) and 5.3% (IQR: 2.4-9.7) respectively. On UofW-LC (124 patients; mean age, 46 years +/- 12 [s.d.]; 73 female), the model had a Dice score of 0.830 +/- 0.107 (CI: 0.798-0.863) and median volume estimation error of 9.7% (IQR: 4.5-15.1). The model showed strong agreement with expert assessments, with r^2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion: The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments.

Shadow and Light: Digitally Reconstructed Radiographs for Disease Classification

In this paper, we introduce DRR-RATE, a large-scale synthetic chest X-ray dataset derived from the recently released CT-RATE dataset. DRR-RATE comprises of 50,188 frontal Digitally Reconstructed Radiographs (DRRs) from 21,304 unique patients. Each image is paired with a corresponding radiology text report and binary labels for 18 pathology classes. Given the controllable nature of DRR generation, it facilitates the inclusion of lateral view images and images from any desired viewing position. This opens up avenues for research into new and novel multimodal applications involving paired CT, X-ray images from various views, text, and binary labels. We demonstrate the applicability of DRR-RATE alongside existing large-scale chest X-ray resources, notably the CheXpert dataset and CheXnet model. Experiments demonstrate that CheXnet, when trained and tested on the DRR-RATE dataset, achieves sufficient to high AUC scores for the six common pathologies cited in common literature: Atelectasis, Cardiomegaly, Consolidation, Lung Lesion, Lung Opacity, and Pleural Effusion. Additionally, CheXnet trained on the CheXpert dataset can accurately identify several pathologies, even when operating out of distribution. This confirms that the generated DRR images effectively capture the essential pathology features from CT images. The dataset and labels are publicly accessible at https://huggingface.co/datasets/farrell236/DRR-RATE.

Automated classification of multi-parametric body MRI series

Multi-parametric MRI (mpMRI) studies are widely available in clinical practice for the diagnosis of various diseases. As the volume of mpMRI exams increases yearly, there are concomitant inaccuracies that exist within the DICOM header fields of these exams. This precludes the use of the header information for the arrangement of the different series as part of the radiologist's hanging protocol, and clinician oversight is needed for correction. In this pilot work, we propose an automated framework to classify the type of 8 different series in mpMRI studies. We used 1,363 studies acquired by three Siemens scanners to train a DenseNet-121 model with 5-fold cross-validation. Then, we evaluated the performance of the DenseNet-121 ensemble on a held-out test set of 313 mpMRI studies. Our method achieved an average precision of 96.6%, sensitivity of 96.6%, specificity of 99.6%, and F1 score of 96.6% for the MRI series classification task. To the best of our knowledge, we are the first to develop a method to classify the series type in mpMRI studies acquired at the level of the chest, abdomen, and pelvis. Our method has the capability for robust automation of hanging protocols in modern radiology practice.

MRISegmentator-Abdomen: A Fully Automated Multi-Organ and Structure Segmentation Tool for T1-weighted Abdominal MRI

Background: Segmentation of organs and structures in abdominal MRI is useful for many clinical applications, such as disease diagnosis and radiotherapy. Current approaches have focused on delineating a limited set of abdominal structures (13 types). To date, there is no publicly available abdominal MRI dataset with voxel-level annotations of multiple organs and structures. Consequently, a segmentation tool for multi-structure segmentation is also unavailable. Methods: We curated a T1-weighted abdominal MRI dataset consisting of 195 patients who underwent imaging at National Institutes of Health (NIH) Clinical Center. The dataset comprises of axial pre-contrast T1, arterial, venous, and delayed phases for each patient, thereby amounting to a total of 780 series (69,248 2D slices). Each series contains voxel-level annotations of 62 abdominal organs and structures. A 3D nnUNet model, dubbed as MRISegmentator-Abdomen (MRISegmentator in short), was trained on this dataset, and evaluation was conducted on an internal test set and two large external datasets: AMOS22 and Duke Liver. The predicted segmentations were compared against the ground-truth using the Dice Similarity Coefficient (DSC) and Normalized Surface Distance (NSD). Findings: MRISegmentator achieved an average DSC of 0.861$\pm$0.170 and a NSD of 0.924$\pm$0.163 in the internal test set. On the AMOS22 dataset, MRISegmentator attained an average DSC of 0.829$\pm$0.133 and a NSD of 0.908$\pm$0.067. For the Duke Liver dataset, an average DSC of 0.933$\pm$0.015 and a NSD of 0.929$\pm$0.021 was obtained. Interpretation: The proposed MRISegmentator provides automatic, accurate, and robust segmentations of 62 organs and structures in T1-weighted abdominal MRI sequences. The tool has the potential to accelerate research on various clinical topics, such as abnormality detection, radiotherapy, disease classification among others.

Decomposing Vision-based LLM Predictions for Auto-Evaluation with GPT-4

The volume of CT exams being done in the world has been rising every year, which has led to radiologist burn-out. Large Language Models (LLMs) have the potential to reduce their burden, but their adoption in the clinic depends on radiologist trust, and easy evaluation of generated content. Presently, many automated methods are available to evaluate the reports generated for chest radiographs, but such an approach is not available for CT presently. In this paper, we propose a novel evaluation framework to judge the capabilities of vision-language LLMs in generating accurate summaries of CT-based abnormalities. CT slices containing an abnormality (e.g., lesion) were input to a vision-based LLM (GPT-4V, LLaVA-Med, and RadFM), and it generated a free-text summary of the predicted characteristics of the abnormality. Next, a GPT-4 model decomposed the summary into specific aspects (body part, location, type, and attributes), automatically evaluated the characteristics against the ground-truth, and generated a score for each aspect based on its clinical relevance and factual accuracy. These scores were then contrasted against those obtained from a clinician, and a high correlation ( 85%, p < .001) was observed. Although GPT-4V outperformed other models in our evaluation, it still requires overall improvement. Our evaluation method offers valuable insights into the specific areas that need the most enhancement, guiding future development in this field.

Self and Mixed Supervision to Improve Training Labels for Multi-Class Medical Image Segmentation

Accurate training labels are a key component for multi-class medical image segmentation. Their annotation is costly and time-consuming because it requires domain expertise. This work aims to develop a dual-branch network and automatically improve training labels for multi-class image segmentation. Transfer learning is used to train the network and improve inaccurate weak labels sequentially. The dual-branch network is first trained by weak labels alone to initialize model parameters. After the network is stabilized, the shared encoder is frozen, and strong and weak decoders are fine-tuned by strong and weak labels together. The accuracy of weak labels is iteratively improved in the fine-tuning process. The proposed method was applied to a three-class segmentation of muscle, subcutaneous and visceral adipose tissue on abdominal CT scans. Validation results on 11 patients showed that the accuracy of training labels was statistically significantly improved, with the Dice similarity coefficient of muscle, subcutaneous and visceral adipose tissue increased from 74.2% to 91.5%, 91.2% to 95.6%, and 77.6% to 88.5%, respectively (p<0.05). In comparison with our earlier method, the label accuracy was also significantly improved (p<0.05). These experimental results suggested that the combination of the dual-branch network and transfer learning is an efficient means to improve training labels for multi-class segmentation.

Automated Plaque Detection and Agatston Score Estimation on Non-Contrast CT Scans: A Multicenter Study

Coronary artery calcification (CAC) is a strong and independent predictor of cardiovascular disease (CVD). However, manual assessment of CAC often requires radiological expertise, time, and invasive imaging techniques. The purpose of this multicenter study is to validate an automated cardiac plaque detection model using a 3D multiclass nnU-Net for gated and non-gated non-contrast chest CT volumes. CT scans were performed at three tertiary care hospitals and collected as three datasets, respectively. Heart, aorta, and lung segmentations were determined using TotalSegmentator, while plaques in the coronary arteries and heart valves were manually labeled for 801 volumes. In this work we demonstrate how the nnU-Net semantic segmentation pipeline may be adapted to detect plaques in the coronary arteries and valves. With a linear correction, nnU-Net deep learning methods may also accurately estimate Agatston scores on chest non-contrast CT scans. Compared to manual Agatson scoring, automated Agatston scoring indicated a slope of the linear regression of 0.841 with an intercept of +16 HU (R2 = 0.97). These results are an improvement over previous work assessing automated Agatston score computation in non-gated CT scans.

Weakly Supervised Detection of Pheochromocytomas and Paragangliomas in CT

Pheochromocytomas and Paragangliomas (PPGLs) are rare adrenal and extra-adrenal tumors which have the potential to metastasize. For the management of patients with PPGLs, CT is the preferred modality of choice for precise localization and estimation of their progression. However, due to the myriad variations in size, morphology, and appearance of the tumors in different anatomical regions, radiologists are posed with the challenge of accurate detection of PPGLs. Since clinicians also need to routinely measure their size and track their changes over time across patient visits, manual demarcation of PPGLs is quite a time-consuming and cumbersome process. To ameliorate the manual effort spent for this task, we propose an automated method to detect PPGLs in CT studies via a proxy segmentation task. As only weak annotations for PPGLs in the form of prospectively marked 2D bounding boxes on an axial slice were available, we extended these 2D boxes into weak 3D annotations and trained a 3D full-resolution nnUNet model to directly segment PPGLs. We evaluated our approach on a dataset consisting of chest-abdomen-pelvis CTs of 255 patients with confirmed PPGLs. We obtained a precision of 70% and sensitivity of 64.1% with our proposed approach when tested on 53 CT studies. Our findings highlight the promising nature of detecting PPGLs via segmentation, and furthers the state-of-the-art in this exciting yet challenging area of rare cancer management.

Automated Classification of Body MRI Sequence Type Using Convolutional Neural Networks

Multi-parametric MRI of the body is routinely acquired for the identification of abnormalities and diagnosis of diseases. However, a standard naming convention for the MRI protocols and associated sequences does not exist due to wide variations in imaging practice at institutions and myriad MRI scanners from various manufacturers being used for imaging. The intensity distributions of MRI sequences differ widely as a result, and there also exists information conflicts related to the sequence type in the DICOM headers. At present, clinician oversight is necessary to ensure that the correct sequence is being read and used for diagnosis. This poses a challenge when specific series need to be considered for building a cohort for a large clinical study or for developing AI algorithms. In order to reduce clinician oversight and ensure the validity of the DICOM headers, we propose an automated method to classify the 3D MRI sequence acquired at the levels of the chest, abdomen, and pelvis. In our pilot work, our 3D DenseNet-121 model achieved an F1 score of 99.5% at differentiating 5 common MRI sequences obtained by three Siemens scanners (Aera, Verio, Biograph mMR). To the best of our knowledge, we are the first to develop an automated method for the 3D classification of MRI sequences in the chest, abdomen, and pelvis, and our work has outperformed the previous state-of-the-art MRI series classifiers.