Jiang Xiaoyu, Washington Mary Kay, Izzy Manhal J, Lu Ming, Yan Xinqiang, Zu Zhongliang, Gore John C, Xu Junzhong
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cancers (Basel). 2025 Apr 1;17(7):1204. doi: 10.3390/cancers17071204.
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.
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.
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.
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.
当前指南推荐对比增强CT/MRI作为诊断肝细胞癌（HCC）的确诊性影像学检查。然而，这些检查方式并不总能将HCC与肝硬化肝脏中常见的良性/发育异常结节区分开来。因此，许多病变需要通过侵入性活检进行病理确诊，或者在3 - 6个月后进行监测成像，这导致诊断和治疗延迟。我们旨在利用磁共振成像（MRI）开发肝细胞大小和细胞密度的非侵入性成像生物标志物，并评估其在识别HCC中的效用。
磁共振细胞术结合了在不同时间测量水扩散速率，这对应于在不同空间尺度探测细胞微观结构。通过将多个扩散加权图像中的体素值拟合到MRI信号的三室（血液、细胞内和细胞外水）模型，得出细胞大小和细胞密度等微观结构特性图。该方法在两个阶段得到验证：（1）组织学驱动的模拟，利用不同肝脏病理的分割组织学图像；（2）对固定的人体肝脏标本进行离体磁共振细胞术。
固定人体肝脏标本的模拟和离体磁共振细胞术均表明，与正常肝脏和肝硬化再生结节相比，HCC的细胞尺寸明显更小，细胞密度更高。
本研究强调了磁共振细胞术通过量化肝脏组织中的细胞大小和细胞密度来区分HCC与非HCC病变的潜力。我们的发现为进一步研究磁共振细胞术在HCC非侵入性早期诊断中的作用提供了坚实基础。
