A Multimodal Imaging Approach for Longitudinal Evaluation of Bladder Tumor Development in an Orthotopic Murine Model

Abstract

Bladder cancer is the fourth most common malignancy amongst men in Western industrialized countries with an initial response rate of 70% for the non-muscle invasive type, and improving therapy efficacy is highly needed. For this, an appropriate, reliable animal model is essential to gain insight into mechanisms of tumor growth for use in response monitoring of (new) agents. Several animal models have been described in previous studies, but so far success has been hampered due to the absence of imaging methods to follow tumor growth non-invasively over time. Recent developments of multimodal imaging methods for use in animal research have substantially strengthened these options of in vivo visualization of tumor growth. In the present study, a multimodal imaging approach was addressed to investigate bladder tumor proliferation longitudinally. The complementary abilities of Bioluminescence, High Resolution Ultrasound and Photo-acoustic Imaging permit a better understanding of bladder tumor development. Hybrid imaging modalities allow the integration of individual strengths to enable sensitive and improved quantification and understanding of tumor biology, and ultimately, can aid in the discovery and development of new therapeutics.

Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment

“…PAI was performed on a Vevo LAZR imaging station (FUJIFILM Visualsonics Inc. Toronto, ON, Canada) which features a hybrid ultrasound and photoacoustic transducer with a tunable nanosecond pulsed laser. Photoacoustic oxygenation signals were collected at 750 and 850 nm and with the provided FUJIFILM Visualsonics imaging analysis software the average oxygen saturation of the hemoglobulin was calculated and visualized [ 30 ].…”

Hand‐held, clinical dual mode ultrasound ‐ photoacoustic imaging of rat urinary bladder and its applications

“…It can be easily combined with other imaging techniques like ultrasound imaging, and fluorescence imaging to facilitate multimodal imaging. Murine urinary bladders were imaged for oxygen saturation computation [38]. PAI uses a pulsed laser as the excitation source; upon absorption of light by the tissue chromophores, there occurs a small temperature rise.…”

“…PAI of canine urinary bladder was studied to determine the presence of muscularis propia invasion. Murine urinary bladders were imaged for oxygen saturation computation [38]. PA imaging was combined with fluorescent imaging for quantification of ICG accumulation in urinary bladder.…”

Insights from animal models of bladder cancer: recent advances, challenges, and opportunities

“…In a recent study, three non-invasive optical imaging modalities including, BLI, HRUS and PAI were combined to increase sensitivity and improve accurate quantification of tumor growth in vivo . This multi-modality evaluation technique provided significant anatomical, molecular, and functional information [ 137 ]. Intensity-focused HIFU uses high-intensity ultrasound waves to precisely treat only the solid malignant tumors with minimal damage to surrounding tissue.…”

“…Imaging and diagnostic approaches described above are valuable means of non-invasive tumor evaluation, specially monitoring response to therapeutics in the live animal. These methods are often coupled and validated with biomarker validation from biological samples in the live animals or with histology and immunohistochemistry from bladder tissues dissected after animal euthanasia [ 137 – 139 ].…”