In vivo quantification of choline compounds in the breast with ¹H MR spectroscopy

Abstract

This work describes a methodology for quantifying levels of total choline-containing compounds (tCho) in the breast using in vivo 1 H MR spectroscopy (MRS) at high field (4 Tesla). Water is used as an internal reference compound to account for the partial volume of adipose tissue. Peak amplitudes are estimated by fitting one peak at a time over a narrow frequency band to allow measurement of small metabolite resonances in spectra with large lipid peaks. This quantitative method significantly improves previously reported analysis methods by accounting for the variable sensitivity of breast 1 H MRS measurements. Using this technique, we detected and quantified a tCho peak in 214 of 500 in vivo spectra. tCho levels were found to be significantly higher in malignancies than in benign abnormalities and normal breast tissues, which suggests that this technique could be used to diagnose suspicious lesions and monitor response to cancer treatments. Breast cancer is a very common disease, affecting 11% of American women and causing more than 40000 deaths each year (1). While breast cancer mortality is decreasing, the incidence continues to rise (2). Thus, there is a great need for noninvasive diagnostic tools for both screening and treatment monitoring. The conventional diagnostics-X-ray mammography, sonography, and physical examination-are limited in their sensitivity for detecting disease and their specificity for distinguishing between benign and malignant lesions. Magnetic resonance imaging (MRI) of the breast is being used increasingly because of its high sensitivity, but its reported specificity is widely variable (3).Researchers have recently begun to augment breast MRI studies with MR spectroscopy (MRS) to increase specificity. In vivo MRS can detect a resonance at 3.25 ppm that has contributions from several different compounds, including choline, phosphocholine, glycerophosphocholine, and taurine. High-resolution in vitro and ex vivo studies indicate that the levels of choline compounds increase with malignancy (4 -6). At the lower field strengths used for in vivo work (1.5-4 T), these multiple resonances cannot be spectrally resolved and thus appear as a single peak, termed total choline-containing compounds (tCho).Several studies conducted at 1.5 T have shown that in vivo MRS can be used to distinguish between benign and malignant tissues (7-11). These studies used the hypothesis that tCho is only detectable in malignancies. A pooled analysis of these five studies showed that this tCho detectability criterion can identify malignancies with an 83% sensitivity and 85% specificity (12). This qualitative approach is promising, but it is only applicable if the MRS measurement sensitivity is invariant. In similar studies performed at 4 T, the increased sensitivity allows detection of tCho in benign lesions and normal subjects. A more general approach is to quantify the tCho peak with the expectation that tCho levels are higher in malignancies than in benign lesions or normal tissues. Two groups have reported quanti...

Neoadjuvant chemotherapy in breast cancer: early response prediction with quantitative MR imaging and spectroscopy

“…Diffusion-weighted MRI can be used to detect changes in the apparent diffusion coefficient (ADC) for tissue water associated with changes in tissue and intracellular structure (Zhao et al, 1996;Gallons et al, 1999;Ross et al, 2003;Moffat et al, 2005). Proton magnetic resonance spectroscopy (MRS) can be used to characterise breast lesions through differences in the ratio of fat and water signals (Chu et al, 1987;Sijens et al, 1988) or the intensity of signal from choline-containing compounds (Bradamante et al, 1988;Katz-Brull et al, 2002;Bolan et al, 2003;Jacobs et al, 2004;Jacobs et al, 2005). Both fat : water ratios (Jagannathan et al, 1998) and choline levels (Preul et al, 2000;Jagannathan et al, 2001;Schwarz et al, 2002;Meisamy et al, 2004) have also been used to monitor treatment-induced changes, and phosphorous MRS has been used to predict response using differences in the levels of phosphocholine or phosphomonoesters (Shukla-Dave et al, 2002a, b;Arias-Mendoza et al, 2004).…”

Magnetic resonance imaging features of fibrocystic change of the breast

“…Raw data acquired was then transferred to a PC and processed by advanced signal processing software. The choline-containing compounds concentration was calculated using water as an internal reference [9,10].…”

1H‐magnetic resonance spectroscopy of the breast at 3.0‐T: Comparison of results obtained before and after administration of gadolinium‐based contrast agent

“…Initially, a simple dichotomous approach based on the presence or absence of the choline peak was shown in some reports (5,6). Furthermore, choline quantification has been proposed using either an internal or an external reference (9,10). Recently, Sardanelli et al (7) showed that breast MRS using the integral value of the choline peak allowed a high level of diagnostic performance, with 84% sensitivity and 89% specificity.…”

“…Regarding the breast, MRS has been shown to be useful for the differentiation between benign and malignant lesions and for the monitoring of early response to neoadjuvant chemotherapy (7)(8)(9). Its diagnostic value for breast cancer is typically based on the detection of elevated levels of choline compounds, which are markers of active tumors (10,11).…”