Impact of CT Intensity and Contrast Variability on Deep-Learning-Based Lung-Nodule Detection: A Systematic Review of Preprocessing and Harmonization Strategies (2020–2025)

<b>Background/Objectives</b>: Lung cancer is the leading cause of cancer-related mortality worldwide, and early detection using low-dose computed tomography (LDCT) substantially improves survival outcomes. However, variations in CT acquisition and reconstruction parameters including Hounsfield Unit (HU) calibration, reconstruction kernels, slice thickness, radiation dose, and scanner vendor introduce significant intensity and contrast variability that undermine the robustness and generalizability of deep-learning (DL) systems. <b>Methods</b>: This systematic review followed PRISMA 2020 guidelines and searched PubMed, Scopus, IEEE Xplore, Web of Science, ACM Digital Library, and Google Scholar for studies published between 2020 and 2025. A total of 100 eligible studies were included. The review evaluated preprocessing and harmonization strategies aimed at mitigating CT intensity variability, including perceptual contrast enhancement, HU-preserving normalization, physics-informed harmonization, and DL-based reconstruction. <b>Results</b>: Perceptual methods such as contrast-limited adaptive histogram equalization (CLAHE) enhanced nodule conspicuity and reported sensitivity improvements ranging from 10 to 15% but frequently distorted HU values and reduced radiomic reproducibility. HU-preserving approaches including HU clipping, ComBat harmonization, kernel matching, and physics-informed denoising were the most effective, reducing cross-scanner performance degradation, specifically in terms of AUC or Dice score loss, to below 8% in several studies while maintaining quantitative integrity. Transformer and hybrid CNN-Transformer architectures demonstrated superior robustness to acquisition variability, with observed AUC values ranging from 0.90 to 0.92 compared with 0.85-0.88 for conventional CNN models. <b>Conclusions</b>: The evidence indicates that standardized HU-faithful preprocessing pipelines, harmonization-aware modeling, and multi-center external validation are essential for developing clinically reliable and vendor-agnostic AI systems for lung-cancer screening. However, the synthesis of results is constrained by the heterogeneous reporting of acquisition parameters across primary studies.