Diffusion-weighted PROPELLER MRI for quantitative assessment of liver tumor necrotic fraction and viable tumor volume in VX2 rabbits

PATIENTS WITH LIVER TUMORS of primary or metastatic origin can undergo a number of potential therapies. Accurate, timely assessment of response is critical to individualize treatment regimens. Anatomic tumor size changes as specified by the Response Evaluation Criteria in Solid Tumors (RECIST) (1) or World Health Organization (WHO) criteria (2) are most commonly used to evaluate response. However, liver tumor response often involves the formation of necrosis without immediate size changes. A noninvasive surrogate for pathology providing necrotic fraction (NF), whole-tumor- volume (WTV), and viable-tumor-volume (VTV) measurements would permit more accurate assessments of therapy response. Accordingly, the European Association for the Study of Liver Disease (EASL) recently proposed measuring posttherapy changes in VTV with contrast-enhanced (CE) CT or MRI (3,4). However, CE CT and MRI measurements may struggle to accurately differentiate viable from necrotic tissues (5–10) and to our knowledge have yet to be validated for VTV measurements in liver tumors. Alternatively, diffusion-weighted MRI (DWI) may permit tissue characterization without the need for exogenous contrast agents. DWI uses local water mobility as an endogenous probe for noninvasive interrogation of tissue microstructure. DWI has been used for detection of liver tumors (11), differentiation of lesion types (12), and detection of microstructural changes after therapy (13). DWI offers the potential to differentiate viable tissues from regions of necrosis based on the difference in local water mobility between these tissues (14). Previous studies demonstrated a strong correlation between tumor NF and mean whole tumor apparent diffusion coefficient (ADC) measurements (15–17). More recently, Carano et al (18) and Henning et al (19) each used DWI to generate spatially resolved tissue viability maps for VTV measurements in murine xenograft human colon and RIF-1 tumor models, respectively. However, to our knowledge no studies have used DWI for in situ VTV or NF measurements in liver tumors. Production of spatially resolved liver tumor viability maps with conventional single-shot DW-SE-EPI approaches may be challenging. Particularly for abdominal applications, single-shot approaches often result in relatively poor overall image quality due to geometric distortion, chemical shift artifacts, and limited spatial resolution (20). Multishot DWI approaches may overcome these limitations (21–24). Multishot DW-PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) approaches were less sensitive to motion artifacts due to the intrinsic properties of segmental phase corrections and oversampling at the central k-space. A recent study using multishot DW-PROPELLER demonstrated significantly improved image quality for abdominal DWI with reduced distortion and artifact levels compared to DW-SE-EPI (25). The purpose of our study was to compare DW-SE-EPI and DW-PROPELLER NF and VTV measurements to reference standard histological measurements in a rabbit VX2 liver tumor model. We tested the hypothesis that DW-PROPELLER provides more accurate liver tumor NF and VTV measurements than conventional DW-SE-EPI.