Specificity of choline metabolites for in vivo diagnosis of breast cancer using 1H MRS at 1.5�T

Abstract

The purpose was to determine if in vivo proton magnetic resonance spectroscopy ((1)H MRS) at 1.5 T can accurately provide the correct pathology of breast disease. Forty-three asymptomatic volunteers including three lactating mothers were examined and compared with 21 breast cancer patients. Examinations were undertaken at 1.5 T using a purpose-built transmit-receive single breast coil. Single voxel spectroscopy was undertaken using echo times of 135 and 350 ms. The broad composite resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), myo-inositol and taurine, was found not to be a unique marker for malignancy providing a diagnostic sensitivity and specificity of 80.0 and 86.0%, respectively. This was due to three of the asymptomatic volunteers and all of the lactating mothers also generating the broad composite resonance at 3.2 ppm. Optimised post-acquisitional processing of the spectra resolved a resonance at 3.22 ppm, consistent with PC, in patients with cancer. In contrast the spectra recorded for three false-positive volunteers, and the three lactating mothers had a resonance centred at 3.28 ppm (possibly taurine, myo-inositol or GPC). This improved the specificity of the test to 100%. Careful referencing of the spectra and post-acquisitional processing intended to optimise spectral resolution of in vivo MR proton spectra from human breast tissue resolves the composite choline resonance. This allows the distinction of patients with malignant disease from volunteers with a sensitivity of 80% and specificity of 100%. Therefore, resolution of the composite choline resonance into its constituent components improves the specificity of the in vivo (1)H MRS method, but does not overcome the problem of 20% false-negatives.

In Vivo Monitoring Response to Chemotherapy of Human Diffuse Large B-Cell Lymphoma Xenografts in SCID Mice by 1H and 31P MRS

“…In contrast, 1 H MRS can detect much smaller tumors (1-2 cm 3 at 1.5 T) with the same signal-to-noise ratio as 31 P MRS at the same acquisition time (25). Proton MRS has been demonstrated to be useful in differentiating between cancer, necrosis, and normal tissue of various organs such as brain (26)(27)(28), prostate (29), neck (28), breast (30,31), kidney (32) and liver (33).…”

Improving proton MR spectroscopy of brain tissue for noninvasive diagnostics

“…An intermediate possibility was recognized: to perform pattern recognition based on a subset of the raw data points, namely chemical shifts expected to represent most common molecular constituents in normal or anomalous brain tissue. No attempt was made to build computational models using only two or three biomarker intensities, which has been done and reported previously (8,9). Instead, alternative ways to access the information in the wider scan range were investigated.…”

“…Work on a variety of tissue types indicates that 1.5T MRS scans contain information useful for diagnostic purposes, particularly biomarkers for N-acetyl aspartate (NAA), choline (Cho), creatinine (Cr), myo-inositol (MI), lactate, and lipids (8,9). However, in brain or other tissues, simple ratios which can distinguish abnormal from normal, ratios like Cho/Cr, cannot adequately distinguish malignant lesions from other features, e.g., progressive multifocal leukoencephalopathy, multiple sclerosis, and stroke (8), or scars in breast tissue (9).…”

“…However, in brain or other tissues, simple ratios which can distinguish abnormal from normal, ratios like Cho/Cr, cannot adequately distinguish malignant lesions from other features, e.g., progressive multifocal leukoencephalopathy, multiple sclerosis, and stroke (8), or scars in breast tissue (9). For a two-category classification model (breast cancer versus scar tissue), Stanwell et al (9) achieved a sensitivity of 80% and specificity of 86% using the multi-compound resonance at 3.2 ppm, which includes contributions from choline, phosphocholine (PC), glycerophosphocholine (GPC), and taurine. In a case of MRS used for diagnosis of Alzheimer's disease, a standard of 80% (0.80) correct relative to autopsy has been reported (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

“…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).…”