Comparison of dynamic contrast-enhanced magnetic resonance imaging and contrast-enhanced ultrasound for evaluation of the effects of sorafenib in a rat model of hepatocellular carcinoma.

OBJECTIVES: To compare the accuracy of contrast-enhanced ultrasound (CEUS) and Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for the assessment of changes in tissue vascularization as result of sorafenib treatment in a rat model of hepatocellular carcinoma (HCC). METHODS: Male Buffalo rats with orthotopic liver tumors treated daily with 7.5 mg/kg sorafenib via oral gavage for 2 weeks (n = 9) were subject to DCE-MRI and CEUS 2 weeks after tumor implantation - right before treatment initiation - and also after treatment completion - right before tumor harvest. Untreated animals (n = 10) were used as control. Tumor tissue sections were stained for hematoxylin-eosin, pimonidazole, and CD34 for quantitative assessment of necrosis, hypoxia, and microvessel density (MVD), respectively. RESULTS: Of all the DCE-MRI parameters that were evaluated, only volume transfer constant (Ktrans) measurements were significantly lower in sorafenib-treated tumors (0.18 vs 0.33 min-1, p < 0.01), indicating a substantial decrease in vascular permeability caused by the therapy. This reduction was associated with decreased MVD (3.9 vs 10.8% CD34+ cells, p < 0.01), higher tumor necrosis (31.9 vs 21.8%, p < 0.001) and hypoxia (19.7 vs 10.5% pimonidazole binding, p < 0.01). Moreover, statistical analysis demonstrate significant correlation of DCE-MRI Ktrans with histopathologic tissue necrosis (r = -0.537, p < 0.05) and MVD (r = 0.599, p < 0.05). Interestingly, none of the CEUS measurements were significantly different between the control and treatment groups, and did not show statistical correlation with any of the histopathological parameters assessed (p > 0.05). CONCLUSIONS: Sorafenib-induced reduction in vascular permeability in this preclinical model of HCC is detected more accurately through DCE-MRI than CEUS, and DCE-MRI parameters strongly correlate with histopathological changes in tissue vascularization and tissue necrosis.

Photoacoustic-based sO2 estimation through excised bovine prostate tissue with interstitial light delivery.

Photoacoustic (PA) imaging is capable of probing blood oxygen saturation (sO2), which has been shown to correlate with tissue hypoxia, a promising cancer biomarker. However, wavelength-dependent local fluence changes can compromise sO2 estimation accuracy in tissue. This work investigates using PA imaging with interstitial irradiation and local fluence correction to assess precision and accuracy of sO2 estimation of blood samples through ex vivo bovine prostate tissue ranging from 14% to 100% sO2. Study results for bovine blood samples at distances up to 20 mm from the irradiation source show that local fluence correction improved average sO2 estimation error from 16.8% to 3.2% and maintained an average precision of 2.3% when compared to matched CO-oximeter sO2 measurements. This work demonstrates the potential for future clinical translation of using fluence-corrected and interstitially driven PA imaging to accurately and precisely assess sO2 at depth in tissue with high resolution.

Photoacoustic imaging driven by an interstitial irradiation source.

Photoacoustic (PA) imaging has shown tremendous promise in providing valuable diagnostic and therapy-monitoring information in select clinical procedures. Many of these pursued applications, however, have been relatively superficial due to difficulties with delivering light deep into tissue. To address this limitation, this work investigates generating a PA image using an interstitial irradiation source with a clinical ultrasound (US) system, which was shown to yield improved PA signal quality at distances beyond 13 mm and to provide improved spectral fidelity. Additionally, interstitially driven multi-wavelength PA imaging was able to provide accurate spectra of gold nanoshells and deoxyhemoglobin in excised prostate and liver tissue, respectively, and allowed for clear visualization of a wire at 7 cm in excised liver. This work demonstrates the potential of using a local irradiation source to extend the depth capabilities of future PA imaging techniques for minimally invasive interventional radiology procedures.