Background and Objectives: Current guidelines recommend contrast-enhanced CT/MRI as confirmatory imaging tests for diagnosing hepatocellular carcinoma (HCC). However, these modalities are not always able to differentiate HCC from benign/dysplastic nodules that are commonly observed in cirrhotic livers. Consequently, many lesions require either pathological confirmation via invasive biopsy or surveillance imaging after 3–6 months, which results in delayed diagnosis and treatment. We aimed to develop noninvasive imaging biomarkers of liver cell size and cellularity, using magnetic resonance imaging (MRI), and to assess their utility in identifying HCC. Methods: MR cytometry combines measurements of water diffusion rates over different times corresponding to probing cellular microstructure at different spatial scales. Maps of microstructural properties, such as cell size and cellularity, are derived by fitting voxel values in multiple diffusion-weighted images to a three-compartment (blood, intra-, and extracellular water) model of the MRI signal. This method was validated in two phases: (1) histology-driven simulations, utilizing segmented histological images of different liver pathologies, and (2) ex vivo MR cytometry performed on fixed human liver specimens. Results: Both simulations and ex vivo MR cytometry of fixed human liver specimens demonstrated that HCC exhibits significantly smaller cell sizes and higher cellularities compared to normal liver and cirrhotic regenerative nodules. Conclusion: This study highlights the potential of MR cytometry to differentiate HCC from non-HCC lesions by quantifying cell size and cellularity in liver tissues. Our findings provide a strong foundation for further research into the role of MR cytometry in the noninvasive early diagnosis of HCC.
背景与目的：当前指南推荐采用增强CT/MRI作为确诊肝细胞癌（HCC）的影像学检查手段。然而，这些影像学方法并不总能有效区分HCC与肝硬化肝脏中常见的良性/异型增生结节。因此，许多病灶仍需通过侵入性活检进行病理学确认，或需在3-6个月后进行监测性影像学检查，导致诊断和治疗延迟。本研究旨在利用磁共振成像（MRI）开发基于肝细胞大小和细胞密度的无创影像学生物标志物，并评估其在识别HCC中的效用。方法：MR细胞计量技术通过测量不同时间尺度的水分子扩散速率，实现在不同空间尺度上探测细胞微观结构。该技术通过将多张扩散加权图像中的体素值拟合至MRI信号的三室模型（血液、细胞内水及细胞外水），从而生成细胞大小和细胞密度等微观结构特征图谱。该方法的验证分为两个阶段：（1）基于组织学的模拟验证，利用不同肝脏病理状态的切片组织图像进行分割分析；（2）对固定人体肝脏标本进行离体MR细胞计量分析。结果：模拟验证与离体标本实验均表明，与正常肝脏及肝硬化再生结节相比，HCC的细胞尺寸显著减小且细胞密度明显增高。结论：本研究揭示了MR细胞计量技术通过量化肝组织细胞大小与细胞密度来区分HCC与非HCC病变的潜力。该发现为深入探索MR细胞计量技术在HCC无创早期诊断中的应用奠定了重要基础。
Distinguishing Hepatocellular Carcinoma from Cirrhotic Regenerative Nodules Using MR Cytometry
肿瘤(癌症)患者之家