Magnetic resonance imaging (MRI) has high sensitivity for detection of breast cancer but low specificity. Qualitative and quantitative measurements of choline containing (tCho) compounds by MR spectroscopy have shown promise in diagnosis as well as in non-invasive therapeutic assessment of breast cancer. Diffusion weighted imaging (DWI) allows mapping of apparent diffusion coefficient (ADC) of tissues. The lower ADC value has been reported in malignant compared to benign disease. Use of these techniques in combination has been documented to increase the specificity of MRI. This talk highlights the role of MRS and DWI in breast cancer management.
Highlights
Target Audience
Scientists, radiologists and clinicians interested in experimental aspects/optimization and clinical applications of breast MRS and diffusion MRI.Outcome/Objectives
Participants will learn about the basics of breast MRS, diffusion mapping in characterization of breast lesions, response assessment using MRS and DWI techniques, experimental consideration and strategies to optimize acquisition and processing of breast MRS and DWI.Purpose/Introduction
Breast cancer is a major cause of cancer related mortality and morbidity in women worldwide. Conventionally X-ray mammography has been the primary diagnostic and screening method but it has limitations of detecting lesion in a dense breast tissue, especially in young women. Diagnosis of breast cancer is confirmed by histopathology of biopsied tissue and cytology of fine needle aspirates in a clinical setting. Over the past two decades, both magnetic resonance imaging (MRI) and MR spectroscopy (MRS) have rapidly evolved as sensitive tools for morphological and biochemical characterization of breast cancer. The MRI has shown potential in resolving indeterminate mammography findings, screening of high risk women, preoperative staging and multi-focal disease [1]. In vivo MRS, is an unique method for acquiring biochemical information from a defined region of interest in a non-invasive manner. Several MRS studies documented a distinct peak due to total choline (tCho) in malignant breast tissue which has been suggested as a biomarker of breast cancer. Inclusion of proton MRS in a clinical setting has been reported to increase the specificity of MRI [2-4]. The monitoring of therapeutic response using tCho levels has also been reported in various breast MRS studies [5-7]. Diffusion weighted imaging (DWI) is based on the measurement of diffusion property of water molecules in tissues and thus it is useful to study changes in tissue density and cellularity. Many studies reported potential applications of DWI in differentiating malignant and benign lesions and monitoring of treatment response [8-10]. This talk will present salient technical aspects of in vivo proton MRS, DWI, their potential and pitfalls in breast cancer management.
Breast MRS
In the past two decades, several studies investigated the use of in vivo 1H MRS in differentiating malignant from benign breast lesions [2-4]. The in vivo 1H MR spectrum (water and fat suppressed) of malignant breast lesion is characterized with an intense peak at 3.2 ppm corresponding to tCho. Elevated levels of tCho has been reported in malignant compared to benign breast lesions [2-4]. The increased tCho was attributed to rapid membrane synthesis associated with tumor proliferation [2-4]. The tCho signal has contributions from N-methyl groups of many Cho containing compounds such as phosphocholine, glycerophosphocholine, and free choline but major component is phosphocholine in breast cancer. Multi-voxel MRS imaging (MRSI) studies have also been reported in differentiation of breast cancer from benign lesions [11]. The major advantages of MRSI are simultaneous assessment of multiple lesions and lesion margins and its intermingling into the surrounding tissues [11]. Studies have also reported semi-quantitative and quantitative measurements of tCho signal in differentiating malignant from benign disease [4,11,12]. Using semi-quantitative method signal-to-noise ratio (SNR) of tCho resonance (ChoSNR) and tCho integral [12] were reported. Recently, the absolute concentration of tCho in locally advanced patients (n=120), early breast cancer patients (n=31), patients with benign lesions (n=38) and controls (n=37) using 1H MRS was reported [4]. The tCho cut-off values were also obtained for the differentiation of malignant from benign breast tissues (2.54 mmol/kg); malignant versus normal (1.45 mmol/kg) and between benign versus normal breast tissues (0.82 mmol/kg) [4]. Studies also reported the observation of tCho in normal breast tissue of lactating women [13]. It was suggested that observation of lactose peak and higher ADC in the breast tissue of healthy lactating women volunteers may distinguish normal lactating breast tissue from malignant tissue [13]. The association of estrogen receptor, progesterone receptor and HER2 status of breast cancer patients with tCho concentration and tumor volume was also investigated [4]. Non-triple negative and triple positive patients showed a significantly higher tCho concentration compared to triple negative patients suggesting molecular heterogeneity of breast lesions. Studies also reported the potential use of W-F ratio and tCho in assessing the effect of neoadjuvant chemotherapy (NACT) in breast cancer [5-7]. Meisamy et al. reported changes in tCho levels within 24 hours of administering chemotherapy, thus showing the potential of tCho as a predictor of therapeutic response [6]. Recently, our group reported that the tCho concentration is a better predictor of early response of breast cancer patients than tumor volume [5]. Also the value of ChoSNR, tumor volume and diameter in the assessment of tumor response in LABC patients undergoing NACT has been demonstrated [5].
Breast DWI
Several studies have documented that ADC of malignant tumors was significantly lower compared to benign lesions and normal tissues due to their increased cellularity [8,9]. However, small cancer foci may not be observed well on ADC maps even under optimal conditions [8,9]. Recently we reported DWI of a total of 203 subjects which included 141 infiltrating ductal carcinoma (IDC) patients, 34 benign breast pathology and 28 normal volunteers who did not have any breast abnormalities. Our data showed that the mean ADC of malignant lesion was significantly lower compared to benign and normal breast tissues [14]. Recent studies have documented that changes in MRI derived parameters like tumor diameter and tumor ADC after first cycle of therapy could provide a valuable tool for early evaluation of treatment response in breast cancer patients [9,10]. Studies documented that DWI is potentially useful in assessing the response to NACT of breast tumors [9,10].
Conclusions
In recent years remarkable growth has occurred in the advancement of MR based techniques for assessment of breast cancer. DWI has the ability for evaluating the cellular changes which can be used for discrimination of malignant and benign lesions. The key feature of in vivo MRS is the ability to measure endogenous metabolites noninvasively as well as changes in metabolic pathways linked with malignancy. Further, MR spectroscopy is also useful for monitoring therapeutic response of tumors. More studies are required to improve the sensitivity and specificity of in vivo MRS and DWI for several types of malignant lesions and also particularly for small lesions before these methods are incorporated in clinical practice.