Clinical optoacoustic imaging combined with ultrasound for coregistered functional and anatomical mapping of breast tumors

Abstract

Optoacoustic imaging, based on the differences in optical contrast of blood hemoglobin and oxyhemoglobin, is uniquely suited for the detection of breast vasculature and tumor microvasculature with the inherent capability to differentiate hypoxic from the normally oxygenated tissue. We describe technological details of the clinical ultrasound (US) system with optoacoustic (OA) imaging capabilities developed specifically for diagnostic imaging of breast cancer. The combined OA/US system provides co-registered and fused images of breast morphology based upon gray scale US with the functional parameters of total hemoglobin and blood oxygen saturation in the tumor angiogenesis related microvasculature based upon OA images. The system component that enabled clinical utility of functional OA imaging is the hand-held probe that utilizes a linear array of ultrasonic transducers sensitive within an ultrawide-band of acoustic frequencies from 0.1 MHz to 12 MHz when loaded to the high-impedance input of the low-noise analog preamplifier. The fiberoptic light delivery system integrated into a dual modality probe through a patented design allowed acquisition of OA images while minimizing typical artefacts associated with pulsed laser illumination of skin and the probe components in the US detection path. We report technical advances of the OA/US imaging system that enabled its demonstrated clinical viability. The prototype system performance was validated in well-defined tissue phantoms. Then a commercial prototype system named Imagio™ was produced and tested in a multicenter clinical trial termed PIONEER. We present examples of clinical images which demonstrate that the spatio-temporal co-registration of functional and anatomical images permit radiological assessment of the vascular pattern around tumors, microvascular density of tumors as well as the relative values of the total hemoglobin [tHb] and blood oxygen saturation [sO2] in tumors relative to adjacent normal breast tissues. The co-registration technology enables increased accuracy of radiologist assessment of malignancy by confirming, upgrading and/or downgrading US categorization of breast tumors according to Breast Imaging Reporting And Data System (BI-RADS). Microscopic histologic examinations on the biopsied tissue of the imaged tumors served as a gold standard in verifying the functional and anatomic interpretations of the OA/US image feature analysis.

Photoacoustic imaging of breast cancer: a mini review of system design and image features

“…Since oxygenated hemoglobin and deoxygenated hemoglobin have different peaks in the NIR region, two wavelengths can be used to measure the oxygen saturation levels. Li et al, 32 Oraevsky et al, 57 Dean-Ben et al, 29 and Diot et al 30 successfully demonstrate this possibility in their imaging systems.…”

“…Oraevsky et al 57 proposed a linear-array-based handheld PA system (Imagio) for functional imaging of breast. The system integrates diffused laser light through fiber bundles placed on either side and an US linear phased array transducer into a handheld probe [ Fig.…”

“…For objects located at 3 cm or farther from the probe and in close proximity to the probe, the lateral resolution decreased to ∼1 mm for Alexandrite laser and ∼0.92 mm for Nd:YAG laser. 57 At a video frame rate of 10 PA/US images per second, co-registered functional PA and B-mode US images are displayed simultaneously in real time. An example of a B-mode US image from the system is shown in Fig.…”

“…The mass was biopsied later and the histology revealed grade III IDC. This work by Oraevsky et al 57 is licensed under a Creative Commons Attribution 4.0 International License.…”

“…64 This leads to higher levels of hemoglobin in the tumor region than that of normal tissue. Li et al, 32 Oraevsky et al, 57 Dean-Ben et al, 29 and Diot et al 30 demonstrated the use of HbT level to identify breast tumor.…”