Estimating breast tumor blood flow during neoadjuvant chemotherapy using interleaved high temporal and high spatial resolution MRI

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Breast cancer is the most common cancer in women worldwide. Survival rates for women who are diagnosed early have improved, but this is not the case with late stage disease 1. Patients with advanced breast cancer often undergo neoadjuvant chemotherapy (NACT), with the aim of reducing tumor size. Nevertheless, a significant proportion of patients do not benefit from the treatment 2, but still suffer from its side effects 3. It is important to identify these patients at an early stage of treatment and, where possible, change their therapy.
Treatment response is currently assessed by a combination of clinical examination and imaging techniques such as mammography, ultrasound, and MRI. However, these techniques are typically limited to evaluating morphological changes, such as tumor diameter 5 and volume 6. It is recognized that changes in physiology, such as tumor blood flow (TBF), precede morphological changes, and this allows an assessment of treatment response at an earlier stage of therapy 7. Since 1990, several studies have demonstrated that it is possible to estimate physiological processes using dynamic contrast–enhanced (DCE) MRI, and many studies have exploited this approach to monitor NACT response, either by semi‐quantitative signal‐time curve characterization or by measurement and modeling of tumor contrast uptake 9.
Despite the promise of DCE‐MRI to monitor treatment response, there has been limited adoption of quantitative MRI techniques into clinical practice. Accurate modeling of tracer kinetic time series requires the use of imaging protocols with high temporal resolution (HTR), and such data are usually acquired at the expense of high spatial resolution (HSR) 14. The American College of Radiology guidelines recommend the acquisition of HSR data: a slice thickness of less than 3 mm with in‐plane spatial resolution of 1 mm (or less), suggesting that a temporal resolution of less than 4 min will suffice for “accurate capture of lesion kinetics” ( In the case of TBF measurement, however, the sampling interval plays a major role with the necessity of acquiring data in both the breasts and a feeding artery 15. A sampling rate of one imaging volume every 2 or 3 s is needed to capture the temporal characteristics of the arterial input function (AIF) during the early passes of the contrast agent bolus, although this sampling rate can be relaxed later in the time course 16.
Some studies simply neglect HSR images or breast coverage to improve the sampling rate 14, whereas others have proposed different approaches to meet these conflicting requirements. A two‐bolus technique was proposed to allow for separate HSR and HTR imaging; however, it significantly increases scanning time and reduces the contrast dose that can be used in each bolus 20. Song et al demonstrated a technique that allows acquisition of HTR images (12–15 s) while simultaneously allowing the reconstruction of HSR images from the same data sets 21. Saranathan et al proposed an acquisition technique that switched between HTR with moderate spatial resolution (9 s; 1.1 × 2.5 × 4 mm) during the contrast agent wash‐in phase and low temporal resolution, but HSR (120 s; 1.1 × 1 × 1.2 mm) during the wash‐out phase 22. Despite these proposals, acquisition rates for estimation of TBF remain suboptimal 16.
An alternative approach to that of Saranathan et al is to acquire HSR and HTR images in an interleaved manner. The use of a dual‐echo multislice acquisition by Grovik et al 23 hampered measurement of the AIF, but enabled DCE‐MRI at HTR while retaining HSR images for clinical use. The purpose of this study is to evaluate the feasibility of quantifying TBF in patients with advanced breast cancer undergoing NACT, using an interleaved DCE‐MR imaging technique.

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