Real-Time Assessment of Tissue Hypoxia <i>In Vivo</i> with Combined Photoacoustics and High-Frequency Ultrasound

Gerling, Marco; Ying, Zhao; Nania, Salvatore; Norberg, K. Jessica; Verbeke, Caroline S.; Englert, Benjamin; Kuiper, Raoul V.; Bergström, Åsa; Hassan, Manal M.; Neeße, Albrecht; Löhr, Matthias; Heuchel, Rainer

doi:10.7150/thno.7996

Cited by 120 publications

(142 citation statements)

References 38 publications

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“…PAI increasingly is being used to map tumor hypoxia and monitor changes in tumor perfusion and oxygenation after treatment (4,5). However, despite widespread interest in its clinical translation, very few studies have validated PAI results with standard radiologic techniques (6,7).…”

Section: Implications For Patient Carementioning

confidence: 99%

Photoacoustic Imaging of Vascular Hemodynamics: Validation with Blood Oxygenation Level–Dependent MR Imaging

Rich¹,

Seshadri²

2015

Radiology

120

112

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).q RSNA, 2014 Purpose:To noninvasively assess vascular hemodynamics with photoacoustic imaging (PAI) and blood oxygenation level-dependent (BOLD) magnetic resonance (MR) imaging in phantoms and in an animal model. Materials and Methods:In vivo studies were performed with institutional animal care and use committee approval. In vitro experiments were performed by using a tissue-mimicking phantom in multiple oxygenation conditions (n = 6) to compare PAI measurements and BOLD MR imaging measurements. PAI and T2-weighted spin-echo-based BOLD MR imaging were performed to assess tumor response to carbogen (95% O 2 , 5% CO 2 ) in mice with head and neck tumors before (n = 11) and after (n = 9) treatment with a vascular disrupting agent (VDA). Two-tailed Pearson correlation analysis was performed to determine the correlation between the parameters measured with PAI and BOLD MR imaging in vitro. Two-tailed paired t tests were used to compare change in tumor hemoglobin oxygen saturation (sO 2 ) levels and BOLD signal in response to carbogen. Changes in PAI and BOLD signal intensity before and after VDA treatment were analyzed for significance by using analysis of variance with repeated measures. Results:Phantom measurements yielded good correlation between photoacoustically derived sO 2 levels and BOLD signal intensity (r = 0.937, P = .005) and partial pressure of oxygen (r = 0.981, P = .005). In vivo hemodynamic response to carbogen was characterized by a significant increase in tumor sO 2 levels (P = .003) and BOLD signal (P = .001).When compared with pretreatment estimates, treatment with VDA resulted in a significant reduction in the tumor hemodynamic response to carbogen at PAI (P = .030). Conclusion:Carbogen-based functional imaging with PAI and BOLD MR imaging enables monitoring of early changes in tumor hemodynamics after vascular targeted therapy.q RSNA, 2014

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Section: Implications For Patient Carementioning

confidence: 99%

Photoacoustic Imaging of Vascular Hemodynamics: Validation with Blood Oxygenation Level–Dependent MR Imaging

Rich¹,

Seshadri²

2015

Radiology

120

112

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“…Additional in vivo studies used spectroscopic photoacoustic imaging to assess total hemoglobin concentration and oxygenation saturation versus histological findings in mice including an orthotopic U87 human glioblastoma model 16 as well as in subcutaneous murine 17 and human 22 breast cancer models. Furthermore, it has been demonstrated that spectroscopic photoacoustic imaging allows visualization of areas of hypoxia in an animal model of pancreatic cancer which correlated well with immunohistochemical hypoxia staining 32. Other tissue chromophores, such as lipids, have also been imaged with spectroscopic photoacoustic imaging and compared to histology both in an atherosclerosis models in rabbits in vivo 13 and in excised human atherosclerotic aortas in an ex vivo study 33.…”

Section: Discussionmentioning

confidence: 84%

Multiparametric Spectroscopic Photoacoustic Imaging of Breast Cancer Development in a Transgenic Mouse Model

Wilson¹,

Bachawal²,

Tian³

et al. 2014

Theranostics

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Objective: To evaluate the potential of multiparametric spectroscopic photoacoustic imaging using oxygen saturation, total hemoglobin, and lipid content to differentiate among four different breast histologies (normal, hyperplasia, ductal carcinoma in situ (DCIS), and invasive breast carcinoma) in a transgenic mouse model of breast cancer development.Materials and Methods: Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mammary glands (n=251) of a transgenic mouse model of breast cancer development (FVB/N-Tg(MMTV-PyMT)634Mul) were imaged using B-mode ultrasound and spectroscopic photoacoustic imaging, analyzed for oxygen saturation, total hemoglobin, and lipid content, and processed for histological analysis. Statistical analysis was performed using one-way ANOVA, two-sample t-tests, logistic regression, and ROC analysis.Results: Eighty-two normal, 12 hyperplastic, 96 DCIS, and 61 invasive breast carcinoma mammary glands were analyzed. Based on spectroscopic photoacoustic imaging, the oxygen saturation of hyperplasia (50.6%), DCIS (43.0%), and invasive carcinoma (46.2%) significantly increased compared to normal glands (35.5%, P <0.0001), while both total hemoglobin (P<0.01), and lipid content (P<0.0008) significantly decreased with advancing histology. In differentiating normal and hyperplasia from DCIS and invasive breast carcinoma, multiparametric imaging of oxygen saturation, lipid content, and raw photoacoustic signal at 750 nm provided an AUC value of 0.770.Conclusion: Multiparametric spectroscopic photoacoustic imaging is feasible and allows detection of differences in concentration of tissue chromophores among different histologies in a transgenic mouse model of breast cancer development.

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“…Tumour oxygenation can be imaged by optical techniques [85, 86], MRI [67, 87–89], photoacoustic techniques [90] and nuclear techniques [91, 92]. These approaches are in most cases based on the detection of haemoglobin saturation using techniques such as BOLD MRI, or accumulation of tracers following a reduction reaction by which the reduced molecule becomes entrapped or bound within tumour cells or tissue, for example with nitroimidazole-based probes.…”

Section: Imaging Biomarkers For the “Hallmarks Of Cancer”mentioning

confidence: 99%

Biomarkers in preclinical cancer imaging

Bernsen

Kooiman

Segbers

et al. 2015

Eur J Nucl Med Mol Imaging

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In view of the trend towards personalized treatment strategies for (cancer) patients, there is an increasing need to noninvasively determine individual patient characteristics. Such information enables physicians to administer to patients accurate therapy with appropriate timing. For the noninvasive visualization of disease-related features, imaging biomarkers are expected to play a crucial role. Next to the chemical development of imaging probes, this requires preclinical studies in animal tumour models. These studies provide proof-of-concept of imaging biomarkers and help determine the pharmacokinetics and target specificity of relevant imaging probes, features that provide the fundamentals for translation to the clinic. In this review we describe biological processes derived from the “hallmarks of cancer” that may serve as imaging biomarkers for diagnostic, prognostic and treatment response monitoring that are currently being studied in the preclinical setting. A number of these biomarkers are also being used for the initial preclinical assessment of new intervention strategies. Uniquely, noninvasive imaging approaches allow longitudinal assessment of changes in biological processes, providing information on the safety, pharmacokinetic profiles and target specificity of new drugs, and on the antitumour effectiveness of therapeutic interventions. Preclinical biomarker imaging can help guide translation to optimize clinical biomarker imaging and personalize (combination) therapies.

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Real-Time Assessment of Tissue Hypoxia In Vivo with Combined Photoacoustics and High-Frequency Ultrasound

Cited by 120 publications

References 38 publications

Photoacoustic Imaging of Vascular Hemodynamics: Validation with Blood Oxygenation Level–Dependent MR Imaging

Photoacoustic Imaging of Vascular Hemodynamics: Validation with Blood Oxygenation Level–Dependent MR Imaging

Multiparametric Spectroscopic Photoacoustic Imaging of Breast Cancer Development in a Transgenic Mouse Model

Biomarkers in preclinical cancer imaging

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