IntroductionOther Section

Natural language processing (NLP) has become an essential tool in radiology, with applications spanning voice recognition, information extraction, labeling, protocol generation, and the creation of research cohorts (1). Recently, transformer models have emerged as the state-of-the-art NLP, demonstrating abilities to process large texts and comprehend context (2,3). Large language models (LLMs), such as generative pre-trained transformer (GPT), are built upon this architecture, exhibiting impressive capabilities in text processing and generation, applicable across various medical domains (4-10).

The use of LLMs in radiology holds promise, with many potential applications that may enhance the efficiency of radiologists’ workflow. These include assistance with radiology referrals review, generation of structured and comprehensive radiology reports, simplifying radiology reports for patient communication, question answering for both patients and clinicians, and supporting differential diagnosis. The models can also enhance discussions in complex case reviews, such as tumor boards, by providing rapid, data-driven insights. Research related tasks include assistance with extraction of information from articles, identification of trends and patterns in large datasets or literature and indexing large amounts of text data.

Differential diagnosis in radiology relies on the accurate identification of imaging patterns. This process requires extensive medical knowledge along with radiological expertise. Such expertise is indispensable for proficient radiologists, enabling them to discern potential diagnoses and thereby guide subsequent treatment strategies. LLMs are capable of rapidly processing large amounts of data. Although lacking radiological practical expertise, some models may have broader literature knowledge than physicians. Consequently, LLMs may occasionally offer contextual information that radiologists might not consider at the time (7-9). The aim of our study was to assess GPT-4 as an assistive tool in providing differential diagnoses in neuroradiology. We present this article in accordance with the GRRAS reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-200/rc).

MethodsOther Section

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional review board of Sheba Medical Center (No. 0143-23-SMC), and individual consent was waived due to retrospective nature of this study.

We selected radiology reports for 60 representative neuroradiology pathologies, prioritizing conditions that typically require differential diagnosis based on imaging appearance. Specifically, a board-certified radiologist (T.S.) identified 20 diagnoses featured in recent radiology oral board examinations, that were also representative of a spectrum of pathophysiologies relevant to clinical practice. For each of the selected diagnoses, we systematically extracted three consecutive reports from our radiology information system (RIS), ensuring a balanced representation. Cases were randomly selected and only those with confirmative pathology results or supported by substantial clinical evidence were included.

Each radiology report was initially reviewed by T.S. to remove identifiable demographic information, ensuring patient confidentiality. Reports in our center are inherently non-structured and exhibit variability, as each radiologist employs a unique reporting style, resulting in heterogenous data. The relevant descriptions from each report were translated into English. T.S reviewed the reports and extracted only pertinent sections that directly related to imaging findings necessary for generating differential diagnoses. These were then input into GPT-4 by Y.B., who requested the model to provide the three most likely differential diagnoses, based on the imaging descriptions provided. This was aimed to ensure that GPT-4’s analysis was focused. GPT-4 was accessed on July 10th, 2023, for the first 20 cases, and again on April 24th, 2024 for the remaining 40 cases, and all responses were obtained on these dates. The exact prompt was: “Can you please read this imaginary clinical brain MRI/CT findings and give the 3 most probable differential diagnoses in a descending probability order”.

Three board-certified neuroradiologists (S.S., Y.W. and C.H.) with at least 10 years of experience each, who were blinded to the diagnoses, were presented with identical texts (only the pertinent sections that were extracted from the reports) and provided the three most likely diagnoses for each case. Neither the neuroradiologists nor GPT were privy to any clinical or demographic details on the patients. It should be noted that the neuroradiologists in this study provided their differential diagnoses based solely on the pattern descriptions, without access to the actual images.

Diagnostic accuracy was assessed by determining whether the actual diagnosis was included in the differential diagnosis provided by GPT and the three radiologists. These accuracies were subsequently compared. The agreement between each radiologist and GPT, as well as among the radiologists themselves, was quantified using the linear weighted Cohen’s kappa (kw) coefficient. The interpretation of the kw coefficient was categorized as follows: <0: poor agreement; 0.01–0.20: slight agreement; 0.21–0.40: fair agreement; 0.41–0.60: moderate agreement; 0.61–0.80: substantial agreement; 0.81–0.99: almost perfect agreement.

ResultsOther Section

Patient demographics

The study included 60 patients, the mean age was 47.8 years, and 65% (13/20) were female. An overview of each patient’s diagnosis and clinical presentation is provided in Table 1.

Table 1

Patient clinical characteristics and diagnosis

MRI, magnetic resonance imaging; ADEM, acute disseminated encephalomyelitis; CJD, Creutzfeldt-Jakob disease; CT, computed tomography; GBM, glioblastoma multiforme; NMO, neuromyelitis optica; PRES, posterior reversible encephalopathy syndrome.

Diagnostic accuracy

GPT-4’s inclusion of the correct diagnosis within the differential diagnoses was observed in 61.7% (37/60) of cases. In contrast, the neuroradiologists achieved accuracy rates of 63.33% (38/60), 70% (42/60), and 73.33% (44/60), respectively. A comparison of diagnostic accuracy rates between GPT and the neuroradiologists relative to the actual diagnoses is depicted in Figure 1. Specific examples of cases are illustrated in Figures 2,3.

Figure 1 GPT-4 and neuroradiologists differential diagnoses success rates. Pie charts describing the performance of GPT-4 and each of the neuroradiologists separately in listing the correct diagnosis in the differential, based on the actual dagnoses of patients. In blue, the final diagnosis is in the first place of the differential diganosis; in orange, the correct diagnosis is listed in the second or third places of the differential diagnosis; and in grey, the correct diagnosis is not listed at all. GPT, generative pre-trained transformer.

Figure 2 An example of MRI of a patient with CJD (patient #4). The MRI report described: diffusion restriction in the caudate and putamen nuclei bilaterally, the pulvinar nucleus of the thalamus on both sides, and the paramedian cortex in fronto-parietal areas bilaterally, left insula, bilateral occipital lobes, bilateral cingulate gyri, and the right hippocampus. There is also hyperintensity signal in the caudate and putamen nuclei bilaterally on FLAIR sequence, and increased signals in the parietal and occipital cortex. The images show a high DWI signal in the left fronto-parietal cortex (A), as well as the caudate, putamen and thalami bilaterally (D) accompanied by a corresponding low ADC signal (B,E), and an elevated signal on the FLAIR series (C,F) within the same regions. GPT-4 omitted CJD from its differential diagnosis, whereas all three neuroradiologists included CJD in their differential diagnosis. MRI, magnetic resonance imaging; CJD, Creutzfeldt-Jakob disease; FLAIR, fluid-attenuated inversion recovery; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient.

Figure 3 An example of non-contrast head CT of a patient with an acute stroke (patient #16). The CT report described extensive cytotoxic edema in the fronto-parietal, posterior temporal, and occipital areas on the left. There are isolated isodense foci within the edema. The image shows hypodensity in the left parieto-occipital area, accompanied by blurring of the white-gray matter border and effacement of the sulci. ChatGPT and all three neuroradiologists identified acute stroke as the primary differential diagnosis. CT, computed tomography; GPT, generative pre-trained transformer.

Agreement analysis

Agreement between GPT and the neuroradiologists on the first differential diagnosis was fair (kw 0.39, 0.34, 0.36, respectively). Among the radiologists, the agreement was fair to moderate (kw 0.42, 0.54, 0.39, respectively). A detailed breakdown of these agreement rates is presented in Table 2.

Table 2

Agreement rates based on kw coefficient

kw, Cohen’s kappa; GPT, generative pre-trained transformer.

Qualitative analysis

In two cases, GPT-4 included the correct diagnosis as the primary differential, whereas the neuroradiologists did not list the correct diagnosis as the first differential. The diagnoses of these cases were herpes encephalitis and pineocytoma. In none of the cases did the LLM include the correct diagnosis in the top three differential when it was omitted by all radiologists. In three instances, involving cases of Creutzfeldt-Jakob disease, epidermoid cyst, and tuberous sclerosis, all three radiologists included the diagnoses in their differential, while the LLM omitted them.

In one case of herpes encephalitis, only one radiologist listed the diagnosis among the top three differentials, placing it third, while the other two did not include it at all. The radiology report described the findings as follows: “In the temporal lobes, areas of damage are demonstrated, more prominent in the right temporal lobe, but also on the lateral side of the left temporal lobe”. The radiologists’ differential diagnosis included old infarcts, chronic traumatic injury, malacia or postoperative changes. The LLM’s differential included herpes simplex encephalitis, Alzheimer’s disease and temporal lobe epilepsy. The LLM’s response is detailed in the Appendix 1 (Case #1).

There were 13 cases where all readers and the LLM included the correct diagnosis in the differential list. One example is a case of cavernoma, described in the report as: “A mottled parenchymal structure in the medial temporal lobe on the left side. A hypointense hemosiderin ring is present around the perimeter. There is a susceptibility effect (blooming) on SWI sequences, and also slightly amorphous internal and peripheral enhancement”. The radiologists’ differential lists included cavernoma, hemorrhagic stroke, a resolving hematoma, hemorrhage within a tumor, and metastases. The LLM’s differential included glioma, cerebral amyloid angiopathy and cavernoma. The response is detailed in Appendix 1 (Case #2).

DiscussionOther Section

This study evaluated GPT’s performance in generating differential diagnoses in neuroradiology based on descriptions from radiology reports. The results show that GPT included the correct diagnosis in 62% of cases, while experienced neuroradiologists had higher accuracy rates. The agreement between GPT and radiologists on the first suggested diagnosis was only slight, and the agreement among radiologists ranged from fair to moderate.

The discrepancies observed between the radiologists and the LLM may be influenced by several factors. One key factor is that the original reports were written by different radiologists with varying reporting styles. Additionally, in cases involving complex pathologies, the LLM may theoretically have an advantage due to its broader general medical knowledge of rare cases compared to neuroradiologists. Conversely, neuroradiologists possess clinical experience and intuition that the LLM lacks. Our qualitative analysis did not reveal any specific patterns in the discrepancies observed. Therefore, a larger study is warranted to determine if any patterns can be identified.

LLMs, such as GPT, offer a new avenue to support various language tasks. Since ChatGPT was first introduced by Open-artificial intelligence (AI) at the end of 2022, other LLMs such as LLaMA, GPT-4, Gemini and Claude have emerged. Numerous studies have explored their applications in healthcare, including clinical decision support, referrals generation, patient question-answering, and research (2,8,11). Our study evaluates the potential of GPT-4 in generation of differential diagnoses in neuroradiology.

LLMs can significantly enhance radiology practice through various potential use-cases (12). These include automated report generation, reducing time radiologists spend on manual reporting while maintaining reporting accuracy and relevancy (13-15). The models can assist in creating structured templates from free text (16). They can also be used to support clinical decision-making, by summarizing research, generating differential diagnoses from textual descriptions (17), and enhancing discussions in complex case reviews such as tumor boards (18). In addition, the models can also be used for generating and reviewing radiology referrals and for protocols’ generation (9). LLMs can be used to improve patient communication and education, by simplifying medical information into understandable language (19). LLMs also serve as conversational agents, providing a user-friendly platform for patient and clinician inquiries, thus improving patient engagement and operational efficiency in everyday clinical work (20). Moreover, in research, LLMs may aid in extracting information from articles, identifying trends in large datasets or literature, and indexing vast amounts of text data (21). All these use cases may contribute to the enhanced efficiency of radiologists’ workflows.

Recent advancements have enabled some LLMs, including GPT-4, to analyze data from both text and images simultaneously. These multimodal models are particularly transformative in healthcare, where medical diagnosis relies on interpreting both textual and visual information. In radiology, this development suggests that the textual descriptions of findings are redundant when using the model, and that the model can analyze images alongside clinical information for a comprehensive patient analysis. However, preliminary research indicates that the current performance of GPT-4 in analyzing radiology images does not yet meet the standards required for clinical applications (22).

Looking ahead, LLMs could enhance patient care and streamline radiologists’ workflow. The multimodal abilities are expected to improve and support studies interpretations while simultaneously generating reports drafts. Furthermore, integrating these models could improve communication between patients and radiologists, thereby enhancing patent education, understanding, and active involvement in care decisions. However, significant challenges remain. These include inherent biases in training data, navigating ethical concerns around AI use in patient care (23), and data security (24). Addressing these limitations while being mindful of the vast potential applications in clinical practice is crucial to developing reliable and applicable tools that can be integrated into routine clinical practice.

The literature generally discusses LLMs as tools to enhance and support healthcare providers, not replace them. Our findings align with this view, as neuroradiologists outperformed GPT in diagnostic accuracy. These models could be valuable for educating radiology residents and supporting less experienced radiologists, especially under time pressure and high workload, which are timely concerns in neuroradiology (25).

Despite the promising potential of LLMs, these models have limitations and risks. They can generate incorrect information, requiring careful validation (26). This is critical in healthcare, where false information can have serious consequences. LLMs may also reinforce existing biases and disparities (27,28). Data security, privacy, and legal responsibility must be considered when using patient data (29). Finally, legal issues related to decisions based on LLM outputs also need careful consideration (26).

This study has several limitations. First, we did not include clinical correlation in the differential diagnosis generation for both GPT and radiologists, focusing only on imaging pattern description. This is because in some cases, incorporating the clinical presentation was highly suggestive of the diagnosis (for instance, stroke). The small sample size and the retrospective nature of the study may also introduce selection bias. Only the pertinent sections of the reports, selected by T.S., were presented to the LLM and the radiologists. T.S. may have been influenced by prior knowledge of the diagnoses, which introduced bias affecting both the LLM and the radiologists. Additionally, we did not evaluate how different prompts, radiologists or report styles affected the performance of the LLM and radiologists. These are potential directions for future studies with larger datasets. We only evaluated a single LLM (GPT-4) and did not compare the performance of different LLMs on this task. In this study, neuroradiologists provided their differential diagnoses based solely on pattern descriptions, without viewing the actual images. Had the neuroradiologists been given access to the studies, it’s plausible their diagnostic accuracy would have improved. Additionally, the level of agreement among them would likely have been higher. Finally, since conducting the study, multimodal capabilities have emerged in LLMs, enabling models like GPT-4 to analyze images in addition to text (24). However, as our research specifically focused on the textual analysis capabilities of GPT-4 and differential diagnosis derived from text-based pattern recognition, we did not incorporate image analysis. Preliminary data suggest that the model’s current performance in radiology image analysis is not yet adequate for clinical applications (22).

ConclusionsOther Section

In conclusion, GPT showed the ability to provide differential diagnoses in neuroradiology based on pattern descriptions from radiology reports. The performance of neuroradiologists surpassed the LLM. While LLMs have potential to enhance daily work and education in radiology, their limitations must be recognized, and they must be used responsibly.

AcknowledgmentsOther Section

The authors acknowledge the use of ChatGPT, an AI language model developed by OpenAI, solely for generating differential diagnoses in this study. The AI-generated diagnoses were compared with those provided by a qualified radiologist to assess their accuracy and reliability. No personal or identifiable patient data was used in this process; all data were anonymized to protect privacy. The authors did not use ChatGPT or any other AI tool for the writing of this manuscript. The authors declare no conflicts of interest and received no funding from OpenAI or related organizations.

Funding: None.

FootnoteOther Section

Reporting Checklist: The authors have completed the GRRAS reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-200/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-200/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by institutional review board of Sheba Medical Center (No. 0143-23-SMC), and individual consent was waived due to retrospective nature of this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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Cite this article as: Sorin V, Klang E, Sobeh T, Konen E, Shrot S, Livne A, Weissbuch Y, Hoffmann C, Barash Y. Generative pre-trained transformer (GPT)-4 support for differential diagnosis in neuroradiology. Quant Imaging Med Surg 2024;14(10):7551-7560. doi: 10.21037/qims-24-200

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