In cancer, monocytes with patrolling-like behavior have been associated with antitumoral effects, but their intravascular motion is currently concealed to noninvasive imaging techniques. This study aimed to evaluate systemic monocyte intravascular patrolling-like behavior during tumor growth, immunotherapy, and splenectomy, using single-cell tracking with preclinical time-lapse brain magnetic resonance imaging (MRI). In a murine syngeneic breast cancer model (4T1, 67NR), time-lapse MRI (repetitive T2*-weighted gradient-echo sequence after in vivo labeling with iron oxide nanoparticles for monocyte detection) of the brain was conducted using a 9.4 T small animal MRI. Control mice were either naive or received sham injections. Additionally, time-lapse MRI was conducted during immunotherapy or following splenectomy in tumor-bearing and tumor-free mice. Individual cells were identified as hypointensities. Tumors were harvested for ex vivo analysis. The number of detected cells within the brain, distant from the tumor, changed during cancer growth. The cell count was significantly lower for tumor-bearing mice compared to controls. In mice bearing 4T1 tumors, the cell count was significantly lower on day 1 and 9 compared to mice bearing 67NR tumors. During immunotherapy, the monocyte count was significantly lower compared to control, but only in the presence of a tumor. Splenectomy reduced the tumor-associated effect on monocyte dynamics in both low- and highly malignant tumors. Based on an exemplary murine breast cancer model, both cancer and immunotherapy change systemic intravascular monocyte patrolling-like behavior early during tumor growth distant from the tumor, an observation that is dependent on the grade of malignancy and the presence of splenic reservoirs. Question Do tumors alter systemic intravascular monocyte dynamics during tumor growth, immunotherapy, and splenectomy at distant sites, and can such changes be detected noninvasively? Findings In murine breast cancer, time-lapse MRI revealed reduced monocyte patrolling-like behavior during tumor growth and immunotherapy, influenced by malignancy grade and splenic reservoirs. Critical Relevance Noninvasive single-cell MRI tracking provides novel insights into systemic immune dynamics in cancer, potentially enabling future monitoring of tumor-immune interactions, therapeutic responses, and immune modulation beyond conventional assessment of tumor burden or tumor microenvironment composition.
To clinically evaluate a fully automated, artificial intelligence-powered, patient-specific biophysical model for predicting radiofrequency ablation (RFA) volumes in hepatocellular carcinoma (HCC) and to compare its performance with manufacturer-provided ablation estimates. This retrospective study included 96 RFA procedures in 65 HCC patients treated using a single ablation with a cluster needle. Tumors, needle position, and postablation zone were manually segmented on periprocedural computed tomography. Liver parenchyma and vascular structures were automatically extracted using deep learning. A graphics processing unit (GPU)-accelerated biophysical model simulated heat transfer, vascular heat-sink effects, and tissue necrosis using patient-specific anatomy and procedural data. Correlations between ablation volume manually segmented and clinical or anatomical parameters (ablation time, ablation tip temperature, tumor–capsule distance, vessel proximity, type, and diameter) were assessed. Model-predicted volumes were compared with ground truth and manufacturer estimates using relative volume difference (RVD) and volume similarity. Final ablation volumes showed wide variability (7.9–78.8 cm³) and were not correlated with any individual clinical or anatomical parameter (Pearson r – 0.02 to 0.29). Across 94 evaluable cases, simulated and ground-truth volumes were similar (p = 0.165), while manufacturer estimates significantly overestimated ablation volume (p < 0.001). The model achieved a median RVD of 0.39 (interquartile range 0.24–0.57), significantly lower than the manufacturer's algorithm (1.04; 0.64–1.61). Incorporating patient-specific ablation time further improved accuracy. Simulation was fast (0.45 s per second of ablation on GPU). A fully automated, patient-specific biophysical model substantially improves RFA ablation volume prediction in HCC compared with manufacturer approximations, supporting its potential role in personalized treatment planning and outcome standardization. Question In patients with hepatocellular carcinoma, can a fully automated, AI-powered, patient-specific biophysical model predict radiofrequency ablation volume more accurately than manufacturer-provided estimates? Findings A fully automated, AI-powered biophysical model integrating patient-specific anatomy and vasculature predicted RFA volume significantly better than manufacturer estimates (median relative volume difference (RVD) 0.39 versus 1.04). Relevance statement Accurate ablation volume prediction could support personalized radiofrequency ablation (RFA) planning, reduce reliance on operator experience, and standardize treatment margins in hepatocellular carcinoma (HCC), potentially improving local tumor control and reducing recurrence in cirrhotic patients undergoing thermal ablation.
This exploratory study assessed the procedural feasibility of in‑bore, real‑time magnetic resonance (MR)‑guided percutaneous irreversible electroporation (IRE) using a clinical 1.5-T system in a porcine model. Three healthy anesthetized juvenile swine underwent IRE in normal renal tissue using a prototype pulse generator and MR-conditional coaxial cannula as electrodes. One swine was ablated twice in the same kidney, resulting in statistically non-independent data. The procedure was guided by a balanced steady-state free precession sequence with orthogonal slices and intermittent position verifications using a radial three-dimensional gradient-echo sequence. Preprocedure radiofrequency noise and signal-to-noise ratio measurements showed slightly increased noise levels in generator standby mode without apparent imaging artifacts. Median procedure time was 48 min with an interquartile range of 17 min. Four hours post-procedure, the treatment zone appeared T1-hypointense in delayed contrast-enhanced imaging. For one treatment zone, hematoxylin and eosin staining (H E), fluorescent terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining (TUNEL), and coregistration to MR imaging were performed. H E showed minor hemorrhaging at the site of electrode insertion. TUNEL demonstrated a strong TUNEL-positive signal correlating with the T1-hypointense signal in delayed contrast-enhanced imaging, with a Dice-Sørensen coefficient of 67
Mismatch repair (MMR) proteins are important in determining therapeutic strategy in endometrial cancer (EC). We investigated the role of microstructural parameters derived from time-dependent diffusion magnetic resonance imaging (td-dMRI) in differentiating MMR status of EC. This prospective single-center study enrolled patients with suspected EC who underwent preoperative td-dMRI. Tumors were classified as MMR-deficient (dMMR) and MMR-proficient (pMMR) by immunohistochemistry. The microstructural parameters, including intracellular volume fraction ( v_in ), cell diameter ( d ), cellularity ( ρ ), extracellular diffusivity ( D_ex ), and water exchange rate constant ( k_in ), were derived by fitting td-dMRI data with three methods (IMPULSED, JOINT, and EXCHANGE), together with the apparent diffusion coefficient (ADC). Differences in these microstructural parameters between dMMR and pMMR EC were compared. The diagnostic performances were evaluated by the areas under the receiver operating characteristic curve (AUC). Eighty-two patients (17 dMMR, 61.8 ± 10.1 years and 65 pMMR, 58.6 ± 11.8 years) were recruited. dMMR EC exhibited higher v_in , ρ and lower D_ex , ADC values than pMMR EC (p ≤ 0.003). IMPULSED and JOINT demonstrated higher AUCs than conventional ADC (p = 0.025 and 0.046, respectively). The combined selected microstructural parameters ( v_in and D_ex ) derived from JOINT achieved an AUC of 0.903; JOINT demonstrated superior parametric stability and marginally better calibration than IMPULSED. In this exploratory study, td-dMRI discriminated between dMMR and pMMR ECs, providing information on the intricate microscopic organizational structures in tumors. The microstructural parameters may serve as a promising method to improve the diagnostic efficacy of diffusion-weighted MRI in differentiating MMR status of EC. Question There remains an unmet need for noninvasive, preoperative tools to assess DNA MMR status in EC. Findings td-dMRI showed significant differences in microstructural parameters between dMMR and pMMR tumors. Relevance statement td-dMRI shows potential as a noninvasive imaging approach for preoperative assessment of MMR status in EC and may support individualized treatment planning.
Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is the clinical diagnostic standard in hepatocellular carcinoma (HCC), but its association with the tumor microenvironment is not fully characterized. In this study, we investigated correlations between DCE-MRI parameters and immunohistochemistry features of HCC. Forty patients, six women and 34 men aged 61.5 ± 10.1 years (mean ± standard deviation) with histologically confirmed HCC were included. DCE-MRI with Gd-EOB-DTPA was performed before surgery, and quantitative parameters were calculated to reflect arterial wash-in, portal venous wash-out and hepatobiliary uptake. Pathological specimens were analyzed for programmed death ligand 1 (PD-L1), glypican-3, CD3+ tumor- and stromal-infiltrating lymphocytes, CD68 and CD34. CD3+ stromal lymphocytes infiltration was inversely correlated with the arterial wash-in (r = -0.47; adjusted p-value = 0.025) and several post-arterial parameters. For the other TME components, only exploratory correlations were identified, none of which were statistically significant after adjustment for multiple testing. CD3+ tumoral infiltration lymphocytes with arterial wash-in (r = -0.35) and transitional phase relative signal intensity (SI) (r = 0.35). Native SI was inversely correlated with PD-L1 (r = -0.32). Difference in SI between the transitional and portal phase correlated with glypican-3 expression (r = 0.32). DCE-MRI shows a moderate association with stromal infiltrating lymphocytes (CD3⁺ SIL) in HCC. Associations with other components of the TME, including tumor-infiltrating lymphocytes (CD3⁺ TIL), PD-L1 and Glypican-3 expression, were observed at uncorrected thresholds, but did not remain statistically significant after correction for multiple testing. Question DCE-MRI constitutes the cornerstone of HCC diagnosis. Is quantitative assessment of wash-in, wash-out and hepatobiliary uptake associated with non-invasive characterization of the TME? Findings CD3⁺ SIL were associated with tumor wash-in and wash-out parameters. Exploratory associations involving CD3⁺ TIL, PD-L1, and glypican-3 lost significance after multiple-testing adjustment. Relevance statement Quantitative DCE-MRI parameters may provide additional non-invasive information regarding tumor tissue characteristics and the tumor microenvironment of HCC.
