Real-time assessment of tissue hypoxia in vivo with combined photoacoustics and high-frequency ultrasound.
OBJECTIVE
In preclinical cancer studies, non-invasive functional imaging has become an important tool to assess tumor development and therapeutic effects. Tumor hypoxia is closely associated with tumor aggressiveness and is therefore a key parameter to be monitored. Recently, photoacoustic (PA) imaging with inherently co-registered high-frequency ultrasound (US) has reached preclinical applicability, allowing parallel collection of anatomical and functional information. Dual-wavelength PA imaging can be used to quantify tissue oxygen saturation based on the absorbance spectrum differences between hemoglobin and deoxyhemoglobin.


METHODS
A new bi-modal PA/US system for small animal imaging was employed to test feasibility and reliability of dual-wavelength PA for measuring relative tissue oxygenation. Murine models of pancreatic and colon cancer were imaged, and differences in tissue oxygenation were compared to immunohistochemistry for hypoxia in the corresponding tissue regions.


RESULTS
Functional studies proved feasibility and reliability of oxygenation detection in murine tissue in vivo. Tumor models exhibited different levels of hypoxia in localized regions, which positively correlated with immunohistochemical staining for hypoxia. Contrast-enhanced imaging yielded complementary information on tissue perfusion using the same system.


CONCLUSIONS
Bimodal PA/US imaging can be utilized to reliably detect hypoxic tumor regions in murine tumor models, thus providing the possibility to collect anatomical and functional information on tumor growth and treatment response live in longitudinal preclinical studies.
1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;
Marco
M
Gerling
2. StratCan Preclinical Cancer Test Facility, Karolinska Institutet, Stockholm, Sweden; ; 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden;
Ying
Y
Zhao
3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden;
Salvatore
S
Nania
3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden;
K Jessica
KJ
Norberg
4. Division of Pathology, Karolinska Institutet, Stockholm, Sweden;
Caroline S
CS
Verbeke
1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;
Benjamin
B
Englert
6. Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska Institutet, Stockholm, Sweden;
Raoul V
RV
Kuiper
1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden;
Asa
A
Bergström
5. Clinical Research Centre, Karolinska University Hospital-Huddinge, Stockholm, Sweden;
Moustapha
M
Hassan
7. Department of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Marburg, Germany.
Albrecht
A
Neesse
1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; ; 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden;
J Matthias
JM
Löhr
1. Center of Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; ; 3. Pancreas Research Laboratory, CLINTEC, Karolinska Institutet, Stockholm, Sweden;
Rainer L
RL
Heuchel
D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D000860:Hypoxia / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging / Q000379:methods; D010101:Oxygen Consumption; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D061088:Photoacoustic Techniques / Q000379:methods*; D014463:Ultrasonography
High-Frequency Ultrasound; Hypoxia.; Photoacoustics