Dynamic Contrast-Enhanced MRI–Derived Intracellular Water Lifetime (τ_i): A Prognostic Marker for Patients with Head and Neck Squamous Cell Carcinomas

Abstract

Background and Purpose Shutter speed model analysis of DCE-MRI allows estimation of τi, a measure of cellular energy metabolism and Ktrans, a measure of hemodynamics. The purpose of this study was to investigate the prognostic utility of pretreatment τi and Ktrans in predicting OS in patients with HNSCC and to stratify p16-positive patients based upon survival outcome. Materials and Methods A cohort of 60 patients underwent DCE-MRI prior to treatment. Median τi and Ktrans values from metastatic nodes were computed from each patient. Kaplan-Meier analyses were performed to associate τi and Ktrans and their combinations with OS for first 2, 5-years and beyond (median duration>7-years). Results By last date of observation, 18 patients had died and median follow-up for surviving patients (n=42) was 8.32-years. Patients with high τi (4-deaths) had significantly (p=0.014) prolonged OS by 5-years compared to those with low τi (13-deaths). Similarly, patients with high τi (4-deaths) had significantly (p=0.006) longer OS at long-term duration than those with low τi (14-deaths). However, Ktrans was a significant predictor for only 5-years follow-up period. There was some evidence (p<0.10) to suggest that τi and Ktrans were associated with OS for first 2-years. Patients with high τi and high Ktrans were associated with significantly (p<0.01) longer OS compared to other groups for all follow-up periods. Additionally, p16-positive patients with high τi and high Ktrans demonstrated a trend towards the longest OS. Conclusions Combined analysis of τi and Ktrans provided the best model to predict OS in HNSCC patients.

Prediction of distant metastases in patients with squamous cell carcinoma of head and neck using DWI and DCE‐MRI

“…Our results are in line with these prior findings as patients with higher pretreatment K trans also did not develop distant metastases. As K trans reflects a combination of tumor perfusion and microvascular permeability, 28 our results and those of earlier published reports 19‐22,26,27 support the notion that tumor vascularity may be an important predictor of disease control in HNSCC. Along with tumor perfusion, hypoxia in tumor tissues is also considered as an important prognostic indicator of response to CRT in HNSCC 42 .…”

“…In the present study, patients who developed distant metastases exhibited lower pretreatment K trans and τ i from the metastatic lymph node compared with those in whom distant metastases did not occur. Higher pretreatment K trans has been reported to predict treatment response to CRT, 19,21,23 induction therapy, 26 and overall survival 20,22,27 in patients with HNSCC, indicating that higher pretreatment K trans is associated with better prognosis. Our results are in line with these prior findings as patients with higher pretreatment K trans also did not develop distant metastases.…”

“…Magnetic resonance imaging (MRI) techniques such as diffusion‐weighted imaging (DWI) and dynamic contrast enhanced (DCE)‐MRI have been used extensively for studying tumor microenvironment and for predicting short and long‐term treatment response as well as overall survival in HNSCC patients 18‐27 . DWI‐derived low‐baseline apparent diffusion coefficient (ADC) 18,21,23‐25 and DCE‐MRI‐derived high‐baseline volume transfer constant ( K trans ) 19‐22,26,27 as well as high mean intracellular water life time ( τ i ) 22 from metastatic neck lymph nodes indicate improved prognosis in patients with HNSCC. However, the prognostic utility of these parameters has not been examined for prediction of distant metastases, which is of major clinical importance in the management of HNSCC patients.…”

The Promise of Novel Biomarkers for Head and Neck Cancer from an Imaging Perspective

“…The temporal imaging is used to develop a concentration-time curve from which several parameter values are derived. One of the most commonly reported, K trans , is a constant of the intravascular efflux of contrast into tumoural interstitial space which has shown a strong predictive association with progress free and overall survival in advanced HNCs [ 57 , 58 ].…”

The Impact of Arterial Input Function Determination Variations on Prostate Dynamic Contrast-Enhanced Magnetic Resonance Imaging Pharmacokinetic Modeling: A Multicenter Data Analysis Challenge, Part II

“…An additional parameter, the mean intracellular water lifetime (τ i ), is used in the SSM to account for the transcytolemmal (cross cell membrane) water-exchange kinetics. Recent studies show that the SSM-derived K trans parameter is a more accurate diagnostic marker for both breast (22, 23) and prostate cancer (24), and pretreatment τ i is predictive of breast cancer response to neoadjuvant chemotherapy (25) and overall survival in patients with head and neck cancer (26). Furthermore, recent results suggest that τ i is potentially a new imaging biomarker of cellular metabolic activity (27–31), specifically the activity of the Na + -K + -ATPase pump, which is essential for all mammalian cells and is primarily responsible for maintaining the K + and Na + gradient in vivo.…”