A Phantom Validation Study Of Photoacoustic/ultrasound Dual-mode Imaging And Its Application In Breast Tumors

Objective:To validate the ability of the photoacoustic(PA)/ultrasound(US)dual mode system to visualize breast phantom vasculature.To validate the ability of the PA/US dual mode system to measure the blood oxygen saturation(SO2)of the phantom blood and explore the effect of vessels depth on the accuracy of PA blood SO2 measurement.Methods:A breast phantom containing mimicking breast tissue,vessels and blood was developed to evaluate the PA/US dual mode system.The vessels were placed in 5 depths ranging from 1.0 cm to 3.0 cm.The SO2 of blood mimics were set at three levels:50%,60%and 70%.PA/US imaging was performed to estimate the SO2 of mimicking blood.The mean error and root mean square error(RMSE)of photoacoustic SO2 measurement of mimic blood at different depths were calculated.The correlation coefficient R between PA estimated SO2 and mimic blood SO2 was also calculated.Results:The hand-held PA/US imaging system can visualize all of the mimicking blood vessels in the depth of 1.0-3.0 cm.The overall mean error of PA estimated SO2 was 0.77%,and the RMSE was 2.81%.The correlation coefficient R between PA estimated SO2 and mimic blood SO2 was 0.962(P<0.001).The RMSE of PA estimated SO2 increased first and then decreased with the increase of depth.Conclusion:The PA/US imaging system has the ability to visualize breast phantom vessels and measure the SO2 of the phantom blood,but the accuracy of SO2 measurement has a depth dependence.Objective:to study and validate the ability of PA/US dual mode imaging system to visualize transplanted breast tumor vessels in nude mice.Methods:Human breast cancer cells MDA-MB-231 were subcutaneously injected into the right pygal of BALB/c mouse to build an breast cancer xenograft model.Xenograft tumors were imaged in vivo using PA/US imaging system.When the tumor volume increased to about 0.2 cm3,0.4 cm3 and 0.6 cm3,three mice were randomly selected for PA/US imaging.The maximum diameter section image of tumor was divided into four regions for photoacoustic signal score.The scoring rules was according to Adler's method for Doppler scoring:Score 1:no PA signals detected or only 1-2 bars of PA signals with a diameter less than 0.1 cm detected;Score 2:3-4 bars of PA signals or a large bar of PA signals penetrating the lesion detected;Score 3:5 or more bars of PA signals or two large bars of PA signals penetrating the lesion detected.After imaging,3 mice were sacrificed to harvest tumor specimens for immunohistochemistry study of CD34.The relation of PA scores between MVD count was analyzed.Results:The breast cancer models of 9 mice were established successfully.16(44.4%)regions scored 1,12(33.3%)regions scored 2,and 8(22.2%)regions scored 3.The correlation coefficient R between PA scores and MVD count was 0.786(p<0.01).Conclusion:The transplanted tumor of triple negative breast cancer(TNBC)in mice showed abundant PA blood flow signals inside the tumor.PA imaging could objectively visualize the tumor blood vessels.There was a linear correlation between PA scores and MVD count.Objective:To investigate the distribution and characteristics of PA signals in different regions of benign and malignant breast nodules using a dual modal PA/US imaging system and establish PA quantitative assessment methods,and investigate their diagnostic efficiency in diagnosing breast cancers.Methods:A total of 14 benign breast nodules and 26 malignant breast nodules were examined by a handheld dual-modal PA/US imaging.system.The volume data were analyzed,the tumor region and peri-tumor region were divided into four parts:Region S:the region surrounding the tumor but within 5 mm from the tumor boundary.Region T:the whole tumor region.Region P:the periphery region inside the tumor and within length L from the tumor boundary,where L is 1/8 of the length of short axis of the tumor.Region C:the central region inside the tumor but not belonging to Region P.A PA scoring system was designed for semi-quantitation of PA signals subsequently.The PA signal density and PA scores of different regions of the benign and malignant nodules were compared,and the diagnostic performances of quantitative and semi-quantitative PA analysis method were evaluated.Results:For both the benign group and the malignant group,the PA signal spacial density and PA scores in either the surrounding or peripheral regions were larger than that of the central region.For both quantitative and semi-quantitative results,significant difference was found in PA signals of the surrounding and peripheral regions comparing with the central regions between benign and malignant tumors,and the difference was significantly lower in benign tumors than that of the malignant ones(PS-T:0.59±0.83 VS 1.82±1.85,P=0.024;PS-C:1.05±1.53 VS 4.01±4.23,P=0.016;PP-C:0.46±0.80 VS 1.45±1.58,P=0.036;SS-T:0.62±0.64 VS 1.25±0.63,P=0.005;SS-C:1.51±0.72 VS 2.14±0.47,P=0.002;SP-C:0.40±0.34 VS 0.83±0.39,P=0.001).The model based on semiquantitative PA scoring method had favorable diagnostic capacity,not inferior to the quantitative analysis.Conclusion:The difference in the distribution of PA signals in different regions of benign and malignant breast lesions was identified.The PA parameters showed good performance in diagnosing breast cancer,indicating the potential of PAI in clinical utilization.