All imaging volumes were centered on the tumor with sections on the horizontal plane and circular saturation bands positioned around the tumor to suppress the signal from formalin. Images were acquired on a clinical 3.0-T MRI unit with maximum gradient strength of 80 mT/m (Achieva Tx Philips Healthcare) by using a body coil for uniform transmission and a 32-channel receiver head coil for high sensitivity signal detection. Tumor skewness was quantified from the histogram distributions obtained from the DWI methods and cellularity. Of the 28 tumors imaged in this study, eight were excluded due to the exclusion criteria of diameter < 15 mm, lobular phenotype, and tumor grading criteria, as reported in the final pathology. Diffusion acquisition 2 was analyzed by using QSI to obtain the full width half maximum (FWHM) of the probability density function. Diffusion acquisition 1 was analyzed by using fitting methods (monoexponential model, stretched exponential model, and diffusion kurtosis imaging ) at DWI to obtain respective measurements of diffusivity. The study design adopted for evaluating q-space imaging (QSI) versus other diffusion-weighted imaging (DWI) techniques for the assessment of tumor cellularity in breast cancer application is shown. Philips Healthcare (Best, the Netherlands) is acknowledged in this study for providing clinical scientist support.įigure 1: Study design. Authors had control of data and information submitted for publication. The study was approved by the North West–Greater Manchester East Research Ethics Committee (identifier: 16/NW/0221) and signed written informed consent was obtained from the participants prior to entry into the study. Participants were enrolled consecutively from Aberdeen Royal Infirmary (Aberdeen, Scotland) between August 2016 and June 2017 ( Fig 1). To test the study hypothesis, we conducted a prospective study in participants with breast cancer on a clinical MRI unit by using a series of DWI examinations performed on whole tumors freshly excised from participants. We therefore hypothesized that measurements of breast tumor cellularity obtained with QSI have a higher effect gradient compared with other existing DWI techniques, and fidelity to the cellularity obtained from histologic analysis. QSI has been shown to be feasible on clinical MRI units because of recent hardware advances meeting the demand on magnetic field gradient, with application demonstrated in brain malignancies ( 22). Q-Space imaging (QSI) eliminates the constraints introduced by modeling approaches, with measurements made directly from the diffusion pattern providing microstructure quantification in the brain ( 19, 20) and sensitive assessment of the changes that arise from malignant transformation ( 21). However, the diffusion measurements obtained from these approaches come from idealistic models of diffusion and are unspecific to underlying tissue features ( 18). Whereas the monoexponential fitting approach reduces the susceptibility of DWI to acquisition configuration ( 14), the diffusion kurtosis imaging (DKI) ( 15) and stretched exponential model (SEM) ( 16) fitting approaches account for the complexity of diffusion in tissue, providing a more accurate representation of diffusion in breast carcinoma ( 17). However, DWI has limited clinical application because of a low measurement-effect gradient and in turn sensitivity to treatment effectiveness ( 11– 13). Patients who positively respond to neoadjuvant chemotherapy treatment show a reduction in tumor cellularity (the percentage of tissue composed of tumor cells), determined as a reduction in the proportion of viable tumor tissue in posttreatment histologic analysis ( 6, 7).ĭiffusion-weighted imaging (DWI) is a conventional radiologic method that provides noninvasive assessment of cellularity by examining the extent that water self-diffusion is confined ( 8, 9), with the proportion of viable tumor cellularity across whole tumors inferred as the amount of skewness present in histogram distributions ( 10). Although a complete pathologic response can be achieved for up to approximately 60% of patients with triple-negative and human epidermal growth receptor 2–positive breast cancers ( 4, 5), a significant proportion of patients progress or show no response to treatment, leading to unnecessary exposure to drug toxicity and delay to surgical intervention. Breast cancer is the most prevalent cancer in women ( 1), with neoadjuvant chemotherapy treatment used before surgery to downstage locally advanced breast tumors and facilitate conservation surgery ( 2, 3).
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