Tumor oxygenation and vascularization are important parameters that determine the aggressiveness of the tumor and its resistance to cancer therapies. We introduce dual-modality ultrasound and photoacoustic imaging (US-PAI) for the direct, non-invasive real-time in vivo evaluation of oxygenation and vascularization of patient-derived xenografts (PDXs) of B-cell mantle cell lymphomas. The different optical properties of oxyhemoglobin and deoxyhemoglobin make it possible to determine oxygen saturation (sO₂) in tissues using PAI. High-frequency color Doppler imaging enables the visualization of blood flow with high resolution. Tumor oxygenation and vascularization were studied in vivo during the growth of three different subcutaneously implanted patient-derived xenograft (PDX) lymphomas (VFN-M1, VFN-M2 and VFN-M5 R1). Similar values of sO₂ (sO₂ Vital), determined from US-PAI volumetric analysis, were obtained in small and large VFN-M1 tumors ranging from 37.9 ± 2.2 to 40.5 ± 6.0 sO₂ Vital (%) and 37.5 ± 4.0 to 35.7 ± 4.6 sO₂ Vital (%) for small and large VFN-M2 PDXs. In contrast, the higher sO₂ Vital values ranging from 57.1 ± 4.8 to 40.8 ± 5.7 sO₂ Vital (%) (small to large) of VFN-M5 R1 tumors corresponds with the higher aggressiveness of that PDX model. The different tumor percentage vascularization (assessed as micro-vessel areas) of VFN-M1, VFN-M2 and VFN-M5 R1 obtained by color Doppler (2.8 ± 0.1%, 3.8 ± 0.8% and 10.3 ± 2.7%) in large-stage tumors clearly corresponds with their diverse growth and aggressiveness. The data obtained by color Doppler were validated by histology. In conclusion, US-PAI rapidly and accurately provided relevant and reproducible information on tissue oxygenation in PDX tumors in real time without the need for a contrast agent.

肿瘤氧合和血管化是决定肿瘤侵袭性及其对癌症治疗抵抗力的重要参数。我们引入了双模态超声和光声成像 (US-PAI)，用于直接、非侵入性实时体内评估 B 细胞套细胞淋巴瘤的患者来源异种移植物 (PDX) 的氧合和血管化。氧合血红蛋白和脱氧血红蛋白的不同光学特性使得使用 PAI确定组织中的氧饱和度 (sO ₂ )成为可能。高频彩色多普勒成像能够以高分辨率显示血流。体内研究了肿瘤氧合和血管化在三种不同的皮下植入患者来源的异种移植 (PDX) 淋巴瘤（VFN-M1、VFN-M2 和 VFN-M5 R1）的生长过程中。从 US-PAI 体积分析确定的类似 sO ₂ (sO ₂ Vital)值在小型和大型 VFN-M1 肿瘤中获得，范围为 37.9 ± 2.2 至 40.5 ± 6.0 sO ₂ Vital (%) 和 37.5 ± 4.0 至 35.7 ± 4.6 sO ₂ Vital (%)，适用于小型和大型 VFN-M2 PDX。相比之下，较高的 sO ₂ Vital 值范围从 57.1 ± 4.8 到 40.8 ± 5.7 sO ₂VFN-M5 R1 肿瘤的重要 (%)（从小到大）对应于该 PDX 模型的更高侵袭性。VFN-M1、VFN-M2和VFN-M5 R1大阶段彩色多普勒（2.8±0.1%、3.8±0.8%和10.3±2.7%）不同肿瘤百分比血管化（评估为微血管面积）肿瘤显然与其多样化的生长和侵袭性相对应。彩色多普勒获得的数据经组织学验证。总之，US-PAI 无需造影剂即可快速准确地实时提供有关 PDX 肿瘤组织氧合的相关且可重复的信息。