Ultrasound Imaging of Breast Tumor Perfusion and Neovascular Morphology

Abstract

In this paper, a novel image processing strategy is detailed for simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. After normalization and tumor segmentation, a global time-intensity curve describing contrast agent flow was analyzed to derive surrogate measures of tumor perfusion (i.e., peak intensity, time-to-peak intensity, area under the curve, wash-in rate, and wash-out rate). Further, a maximum intensity image was generated from these same segmented image sequences and each vascular component was skeletonized via a thinning algorithm. This skeletonized dataset and collection of vessel segments were then investigated to extract parameters related to the neovascular network and physical architecture (i.e., vessel-to-tissue ratio, number of bifurcations, vessel count, and average vessel length and tortuosity). An efficient computation of local perfusion parameters is also introduced and operates by averaging time-intensity curve data over each individual neovascular segment. Each skeletonized neovascular segment is then color-coded by these local measures to produce a parametric map detailing spatial properties of tumor perfusion. Longitudinal DCE-US image datasets were collected in 6 patients diagnosed with invasive breast cancer using a Philips iU22 ultrasound (US) system equipped with a L9-3 MHz transducer and Definity contrast agent. Patients were imaged using US before and after contrast agent dosing at baseline and again at weeks 6, 12, 18, and 24 after treatment started. Preliminary clinical results suggest that breast tumor response to neoadjuvant chemotherapy may be associated with temporal and spatial changes in DCE-US derived parametric measures of tumor perfusion. Moreover, changes in neovascular morphology parametric measures may also help identify any breast tumor response (or lack thereof) to systemic treatment. Breast cancer management from early detection to therapeutic monitoring is currently undergoing profound changes. The development of novel imaging techniques that are sensitive to the unique biological conditions of each individual tumor represent valuable tools in the pursuit of personalized medicine.

Hyposialylated IgG activates endothelial IgG receptor FcγRIIB to promote obesity-induced insulin resistance

“…DCE-US was performed on the proximal hind limb adductor muscle group (adductor magnus and semimembranosus) at baseline and toward the end of a 2-hour hyperinsulinemic-euglycemic clamp entailing an insulin infusion at 20 mU/Kg/min (46)(47)(48)(49). Isoflurane anesthesia was given, a right jugular vein catheter was placed for infusions, and the rectal temperature was maintained at 36. as described previously (40).…”

“…infusion of contrast media (2.5 × 10 7 microbubbles in 100 μl saline) administered by infusion pump. Regions-of-interest (ROI) were defined, and average time-intensity curves were generated and analyzed to extract measurements of CBV (Ipk), MBF (Tpk and WIR), and both CBV and MBF (AUC; and WOR) (46)(47)(48)51). Human subjects.…”

In vitro methods to study bubble-cell interactions: Fundamentals and therapeutic applications

“…1 They are now used in routine clinical practice for echocardiography and increasingly for other indications 2 including the quantification of biological parameters such as blood perfusion rate and hypoxia, 3 which are two important indicators of tumor malignancy. 4 Advances in the understanding of cell and tissue-specific molecular markers have also led to the development of functionalized microbubbles, which are currently being investigated for targeted molecular imaging.…”

Multi-frame rate plane wave contrast-enhanced ultrasound imaging for tumour vascular imaging and perfusion quantification

“…Contrast enhanced ultrasound (CEUS) imaging has shown exciting potential in imaging angiogenesis and flow dynamics [2], [3]. Microbubble contrast agents significantly enhance the acoustic signals within the vessels thus offering substantial benefits for quantitative flow and perfusion measurements [4], [5].…”