tCho Peak Research Articles

Multiparametric Approach with Dynamic Contrast-Enhanced Mri, Diffusion-Weighted Imaging and Mrs of The Breast in Assessment of Suspicious Breast Lesions

Introduction: Breast cancer is the most invasive malignant tumour in females worldwide and is the second leading cause of cancer death in females after lung cancer. In Egypt, cancer breast is the first common site of tumours among females (32%) and the second common tumour site in both sexes. The aim of this study was to evaluate and compare the diagnostic performance of quantitative parameters derived from diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and magnetic resonance spectroscopy (MRS) with ultrasound +/- conventional mammography in differentiating suspicious breast masses (BI-RADS III and IV) and to suggest the most accurate imaging combination for early diagnosis and treatment of cancer breast. Materials and Methods: The study included 40 patients with suspicious breast lesions detected by clinical examination, ultrasound+/- mammography . Dynamic MRI study was performed using 1.5T MRI. Lesions were analyzed regarding their morphology, kinetic curve pattern, ADC value and tCho peak measurement. The results of each MRI parameter were correlated to histo-pathology. Results: In this study sensitivity of sono-mammography was 70% and its specificity was 66.6%. According to using MRI sensitivity was 90% and specificity was 80% by using morphological and curve patterns. As regarding MRS sensitivity was 50% and specificity was 86.7%. Regarding sensitivity of ADC was 90%while its specificity was 93%. The cut off ADC value was 0.95 x 10−3 mm2/s. By using MRI with additive modalities (ADC and MRS) sensitivity was 100% and specificity was 93%. Conclusion: In comparison with MRI, sonomammography alone lack both sensitivity and specificity in detection of breast lesions in suspicious cases. MRI with additive modalities (ADC and MRS) is the best imaging modality in detection of malignant cases and exclusion of benign cases.

Differential diagnosis of plasma cell mastitis and invasive ductal carcinoma using multiparametric MRI.

Evaluate the potential of multiparametric magnetic resonance imaging (MRI) for the differential diagnosis of plasma cell mastitis (PCM) and invasive ductal carcinoma (IDC). A total of 465 female patients, including 197 PCM (42.4%) and 268 IDC (57.6%), were examined using breast MRI scanning using routine sequences, dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI) and MR spectroscopy (MRS). The MRI features of PCM and IDC lesions were analyzed and compared to the histological results. Compared to IDC, the PCM lesions were more frequent in the subareolar regions, hyperintense on T2WI (P<0.01) and showed an initial signal increase ≤90%, a persistent and plateau pattern of time-intensity curves, non-mass enhancement, multiple rim enhancements, central hyperintensity on DWI, a higher ADC value, and total choline (tCho) peak negative and tCho peak integral <29.95 AU (P<0.01). The following breast-associated findings were also observed frequently in PCM: Ipsilateral breast enlargement, nipple retraction, skin thickening, peripheral edema and axillary lymphadenopathy. However, no significant difference was observed between the two groups for the shape, border and adjacent vessel signs of the lesion. Some of the MRI features of PCM and IDC lesions were different. An integrated analysis of these multiparametric MRI features can thus assist in the differential diagnosis of PCM and IDC lesions.

Magnetic Resonance Spectroscopy in the Diagnosis and Prognosis of Breast Cancer

Objective. To evaluate the efficiency of magnetic resonance spectroscopy in the diagnosis and prognosis of breast cancer (BC).Material and methods. Twenty-eight patients aged 37 to 80 years with established primary invasive BC were examined. Its grade was determined according to pathomorphological verification with immunohistochemical analysis. Breast MRI was performed using the standard protocol, by determining the measured diffusion coefficient (MDC), dynamic contrast enhancement (DCE). Proton magnetic resonance spectroscopy was carried out using the Breeze software package. The clinical and morphological findings and the results of radiation studies were compared to determine Nottingham prognostic index (NPI) scores. To identify the Spearman rank correlation coefficient between MRI findings (the type of pharmacokinetic curves, the total choline-containing (tCho) peak integral) and the values characterizing tumor size and grade.Results. NPI calculation showed that the scoring range was 2.4 to 6.76; the expected 5-year survival rates reached 93%. The mean MDC was 0.856×10-3 mm2/sec; type II pharmacokinetic curve prevailed (n=16; 57.1%). There was a statistically significant negative correlation between the values of MDC, the type of a contrast agent accumulation curve, the levels of HER2/neu and the proliferation marker Ki-67; there was a statistically significant strong positive correlation between the presence of 1H-MPC tCho peak and the indicators determining tumor malignancy (the levels of HER2/neu and Ki-67). Statistically significant differences between the type of a pharmacokinetic curve in DCE and the level of tCho in the prognostic groups defined when calculating NPI were determined in patients with moderate (n=4; 14.2%) and poor (n=10; 35.7%) prognosis.Conclusion. The capabilities of MR spectroscopy are superior in information content to the data obtained by determining the MDC, the nature of contrast medium accumulation in breast tumor, and are comparable with the data determining the type of a tumor (the presence of the HER2/neu gene, Ki-67 proliferation marker) in predicting BC cancer grade and 5-year survival rates.

Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study

BackgroundTo evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC).MethodsAfter institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval.ResultsAll spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3–2.4) on day 7, 0.9 (0.4–1.2) on day 14, and 0.4 (0.2–0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2–1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001).ConclusionsA tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4–0.9 mM, constant over the MC and independent of OC use.

Multi-parametric dynamic contrast enhanced MRI, diffusion-weighted MRI and proton-MRS in differentiation of benign and malignant breast lesions: Imaging interpretation and radiology-pathology correlation

ObjectivesComparing the diagnostic accuracy of different MRI techniques in characterization of breast lesions. MethodsThe study was performed using 1.5T MRI and included 35 females with detected 47 breast lesions. Lesions were analyzed regarding their morphology, kinetic curve pattern, DWI and tCho peak measurement. The results of each MRI parameter were correlated to histo-pathology. ResultsThe study included 35 females with 47 breast lesions. Sensitivity and specificity were 87.5% and 93.3% using morphology alone. By using curve pattern, they were 96.9% and 73.3%. DWI was 96.9% sensitive, 66.7% specific, and MRS was 74.2% sensitive and 71.4% specific. The cut-off ADC value was 1.063 × 10−3 mm2/s. Choline cut-off value was (0.36 mmol/l). Sensitivity and specificity were increased to 100% and 93.3% after combining either kinetic curve or DWI with morphology. Sensitivity was increased to 90.3%, after combining MRS with morphology, however this slightly reduced the specificity to 92.9%. ConclusionMRI is very sensitive for detection of breast lesions, however it lacks specificity. Post-processing tools and functional MRI have improved the specificity. MRS has increased the sensitivity, however specificity has been slightly decreased. Advances in knowledgeFunctional MRI is very helpful for characterization of different breast lesions, thus avoiding unnecessary intervention.

1H-MR spectroscopy of suspicious breast mass lesions at 3T: a clinical experience.

To test 3T proton magnetic resonance spectroscopy (1H-MRS) for breast mass lesions. Patients with BI-RADS 4-5 lesions at mammography/ultrasound were prospectively enrolled. After contrast-enhanced breast MRI, single-voxel MRS (point-resolved volume selection, PRESS); pencil-beam shimming; volume of interest 1cm3; TR/TE=3000/135ms) was performed. Spectra were considered reliable if the full width at half maximum (FWHM) of the water peak was ≤45Hz. A signal-to-noise ratio of the total choline (tCho) peak at 3.21ppm ≥2 was used as cutoff for malignancy. All lesions underwent needle sampling. Final pathology was available for all malignant lesions; for benign lesions the reference standard was final pathology or at least 1-year negative follow-up. Reliable spectra were obtained in 115/127 lesions (91%), with a mean FWHM of 32.4Hz (range 8-45Hz). A tCho peak SNR ≥2 was detected in 66 malignant lesions (62 invasive cancers; 4 ductal carcinoma in situ) and in 3 benign lesions. Excluding lesions located ≤1cm from the skin (n=3) or pectoral muscle (n=11), sensitivity was 65/73 [89%, 95% confidence interval (CI): 80-95%], and specificity 25/28 (89%) (95% CI: 72-98%). Considering only invasive cancers, sensitivity reached 61/68 (90%, 95% CI: 81-96%). MRS additional time was 8min. When lesions close to the skin or pectoral muscle are excluded, 3T 1H-MRS of mass lesions ≥1cm showed a high diagnostic performance, however, insufficient to avoid needle biopsy.

Comparative Investigation of Single Voxel Magnetic Resonance Spectroscopy and Dynamic Contrast Enhancement MR Imaging in Differentiation of Benign and Malignant Breast Lesions in a Sample of Iranian Women.

To make a comparison of single voxel magnetic resonance spectroscopy (SV-MRS) and dynamic contrast enhancement (DCE) MRI for differentiation of benign and malignant breast lesions in a sample of Iranian women. A total of 30 women with abnormal breast lesions detected in mammography, ultrasound, or clinical breast exam were examined with DCE and SV-MRS. tCho (total choline) resonance in MRS spectra was qualitatively evaluated and detection of a visible tCho peak at 3.2 ppm was defined as a positive finding for malignancy. Different types of DCE curves were persistent (type 1), plateau (type 2), and washout (type 3). At first, lesions were classified according to choline findings and types of DCE curve, finally being compared to pathological results as the standard reference. this study included 19 patients with malignant lesions and 11 patients with benign ones. While 63.6 % of benign lesions (7 of 11) showed type 1 DCE curves and 36.4% (4 of 11) showed type 2, 57.9% (11of 19) of malignant lesions were type 3 and 42.1% (8 of 19) type 2. Choline peaks were detected in 18 of 19 malignant lesions and in 3 of 11 benign counterparts. 1 malignant and 8 benign cases did not show any visible resonance at 3.2 ppm so SV-MRS featured 94.7% sensitivity, 72.7 % specificity and 86.7% accuracy. The present findings indicate that a combined approach using MRS and DCE MRI can improve the specificity of MRI for differentiation of benign and malignant breast lesions.

Preliminary observations and clinical value of lipid peak in high-grade uterine sarcomas using in vivo proton MR spectroscopy

To retrospectively evaluate the clinical significance of the lipid peak in in vivo proton magnetic resonance spectroscopy (MRS) for the diagnosis of high-grade uterine sarcomas. MRS was performed in patients with 38 pathologically diagnosed uterine corpus tumours (26 leiomyomas and 12 sarcomas) at 3T. Single-voxel MRS data were collected from a single square volume of interest that encompassed the tumours. The concentrations of lipid and total choline compounds (tCho) were classified as high, low or none. High lipid peaks were observed in all 12 sarcomas and not in benign leiomyomas except for 1 lipoleiomyoma. All 26 leiomyomas and 10 of the 12 sarcomas showed tCho peaks, whereas 2 sarcomas with massive necrosis showed no tCho peak. The presence of a high lipid peak for the diagnosis of sarcoma had a sensitivity of 100%, specificity of 96%, positive predictive value of 92% and negative predictive value of 100%. The high lipid peaks in high-grade malignant tumours may be observed in both viable and necrotic areas, and may be useful in distinguishing uterine sarcomas from benign leiomyomas. • High lipid peak on MR spectroscopy is suggestive of uterine sarcomas. • Lipid peak is observed in both viable and necrotic areas in sarcomas. • MR spectroscopy may be useful in distinguishing uterine sarcomas from benign leiomyomas.

Improved diagnostic accuracy in differentiating malignant and benign lesions using single-voxel proton MRS of the breast at 3 T MRI

To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV (1)H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes. A prospective study of SV 1H MRS was performed following dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 61 women using a 3 T MR system. All lesions (n=57) were analysed for characteristics of morphology, contrast-enhancement kinetics, and tCho peak heights at SV (1)H MRS that were two-times above baseline. Subsequently, the tCho in selected lesions (n=32) was quantified by calculating the area under the curve, and a tCho concentration equal to or greater than the cut-off value was considered to represent malignancy. The relationship between tCho in invasive ductal carcinomas (IDCs) and their Bloom & Richardson grading of malignancy was assessed. Fifty-two patients (57 lesions; 42 malignant and 15 benign) were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of predicting malignancy were 100, 73.3, 91.3, and 100%, respectively, using DCE-MRI and 95.2, 93.3, 97.6, and 87.5%, respectively, using SV (1)H MRS. The tCho cut-off for receiver operating characteristic (ROC) curve was 0.33mmol/l. The relationship between tCho levels in malignant breast lesions with their histopathological subtypes was not statistically significant (p=0.3). Good correlation between tCho peaks and malignancy, enables SV (1)H MRS to be used as a clinically applicable, simple, yet non-invasive tool for improved specificity and diagnostic accuracy in detecting breast cancer.

Quantitative mapping of total choline in healthy human breast using proton echo planar spectroscopic imaging (PEPSI) at 3 Tesla

To quantitatively measure tCho levels in healthy breasts using Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI). The two-dimensional mapping of tCho at 3 Tesla across an entire breast slice using PEPSI and a hybrid spectral quantification method based on LCModel fitting and integration of tCho using the fitted spectrum were developed. This method was validated in 19 healthy females and compared with single voxel spectroscopy (SVS) and with PRESS prelocalized conventional Magnetic Resonance Spectroscopic Imaging (MRSI) using identical voxel size (8 cc) and similar scan times (∼7 min). A tCho peak with a signal to noise ratio larger than 2 was detected in 10 subjects using both PEPSI and SVS. The average tCho concentration in these subjects was 0.45 ± 0.2 mmol/kg using PEPSI and 0.48 ± 0.3 mmol/kg using SVS. Comparable results were obtained in two subjects using conventional MRSI. High lipid content in the spectra of nine tCho negative subjects was associated with spectral line broadening of more than 26 Hz, which made tCho detection impossible. Conventional MRSI with PRESS prelocalization in glandular tissue in two of these subjects yielded tCho concentrations comparable to PEPSI. The detection sensitivity of PEPSI is comparable to SVS and conventional PRESS-MRSI. PEPSI can be potentially used in the evaluation of tCho in breast cancer. A tCho threshold concentration value of ∼0.7 mmol/kg might be used to differentiate between cancerous and healthy (or benign) breast tissues based on this work and previous studies.

Enhanced choline metabolism in a rodent rhabdomyosarcoma model: correlation between RT-PCR and translational 3 T H-MRS

PurposeTo investigate which transmembrane choline transporters and intracellular choline kinases play a prominent role at gene expression level in the rise of the total choline (tCho) peak at proton MR spectra in a rodent rhabdomyosarcoma model. Materials and MethodsTwenty-two rats bearing grafted bilateral syngenic rhabdomyosarcoma were examined on a clinical 3 T MR system. Total choline concentration was measured from proton MR spectra using cubic centimeter volumes of interest (VOIs) located contiguously along the greater axis of the tumour. After euthanasia, cubic centimetre tissue specimens corresponding to Proton magnetic resonance spectroscopy (H-MRS) VOIs were frozen in liquid nitrogen. Out of 89 H-MRS voxels, only 39 with a corresponding tissue specimen suitable for biochemical processing were included in the analysis. RNA was extracted from all the 39 samples and reverse-transcribed into cDNA. Choline kinase α and β gene expression as well as genes of the transmembrane transporters OCT1, OCT2, OCT3, CTL1, CTL3, CTL4 and CHT1 were studied using reverse transcriptase polymerase chain reaction. The expression level of each gene (ΔCt), was normalized referred to that of the RPL19 gene. The Spearman rank correlation coefficient was used to analyse variables. ResultsThere was no overexpression of genes coding for kinases; however, significant correlation was observed between kinase α sub-type and the tCho peak (P=.002; r=0.51). OCT1 was the most overexpressed transporter gene. Less overexpressed CTL1 gene was significantly correlated with the tCho peak (P=.02; r=0.38). ConclusionCholine transporters seem to play a predominant role in the increase in total choline concentration at the gene expression level in our model.

Magnetic Resonance Spectroscopy of the Breast at 3T: Pre- and Post-Contrast Evaluation for Breast Lesion Characterization

Purpose. To determine whether in vivo proton magnetic resonance spectroscopy at 3T can provide accurate breast lesion characterization, and to determine the effect of gadolinium on the resonance of tCho. Methods. Twenty-four positive-mammogram patients were examined on a 3T MR scanner. 1H-MRS was performed before and after gadolinium administration. tCho peak was qualitatively evaluated before and after contrast injection. Results. Fourteen out of 27 lesions proved to be malignant after histopathological diagnosis. Using 1H-MRS, before contrast injection, 6/14 confirmed malignancies and 11/13 benign lesions were correctly classified; while, after contrast injection, 11/14 confirmed malignancies and 12/13 benign processes were correctly classified. Post gadolinium 1H-MRS proved useful in picking up tCho signal, improving the overall accuracy, sensitivity, and specificity by 35%, 83%, and 9%, respectively. Conclusion. 1H-MRS overall accuracy, sensitivity, and specificity in detecting breast lesion's malignancy were increased after gadolinium administration. It is prudent to perform 1H-MRS before contrast injection in large breast lesions to avoid choline underestimation. In cases of small or non-mass lesions, it is recommended to perform 1H-MRS after contrast injection for better voxel prescription to enable a reliable preoperative diagnosis.

Differentiation of benign and malignant uterine corpus tumors by using proton MR spectroscopy at 3T: preliminary study

To retrospectively evaluate the diagnostic ability of magnetic resonance (MR) spectroscopy for distinguishing benign and malignant lesions in patients with uterine corpus tumours at MR imaging. Pelvic MR spectroscopy was performed in patients with pathologically diagnosed benign and malignant uterine corpus tumours at 3T-MR imaging. Single-voxel MR spectroscopy data were collected from a single square volume of interest that encompassed the uterine corpus lesion. The total choline compounds (tCho) resonance peak areas were quantified relative to unsuppressed water using a software package. Patients who fulfilled the criteria for estimates of acceptable reliability were included. A total of 32 patients (age range, 24-76 years) with 32 lesions were evaluated in this study. The median lesion size at MR imaging was 50 mm (range, 19-218 mm). A tCho peak was present in all 32 lesions including 14 malignant lesions (9.21 ± 2.21 mM), and 18 benign lesions (4.59 ± 2.22 mM) (p < 0.0001). Using a cut-off value of 7.00 mM for malignant lesions had a sensitivity of 93%, specificity of 83%, PPV of 81% and NPV of 94%. Proton MR spectroscopy with quantitative evaluation of tCho concentration can provide helpful information in distinguishing benign and malignant uterine corpus tumours.

Usefulness of Multimodal Investigations of the Choline Pathway

We feel very appropriate the present comments of Sandi Kwee and colleagues [1] on our experimental work comparing total choline concentration at H-MRS and choline uptake at [F]-fluoromethylcholine (FCH) [2]. As stated by Kwee et al., the so-called total choline peak (tCho) adds different metabolites having a common quaternary ammonium chemical group, prominently choline (Cho), phosphocholine (PC), and glycerophosphocholine [3]. Concentration and contribution of those different molecules can only be determined by high-resolution spectra at very high field strength from cellular extract in experimental settings. We fully agree with Kwee and colleagues when they hypothesize that tissue concentration of PC should have putatively better correlation to FCH uptake than tCho did. However, an a priori governing our work was to perform investigational experiments in a pre-clinical setting, therefore using an in vivo model and a clinical 3 T imager to allow easier translation to human patients’ cohorts in a further step. The major penalty we had then to assume using such system was its inability to separate the different sub-peaks of the ‘full’ tCho peak. However, we remain strongly convinced that the tCho peaks we obtained at 3 T significantly reflected tumor physiology as PC has been identified as the major choline component of H spectra [4, 5]. Thus far, the correlation between [F]-fluoromethylcholine uptake with tCho peak should remain an accurate indicator of what the correlation between FCH uptake and specific PC peak would have been. Furthermore, Al Saffar et al. observed that decrease in tCho and decrease in PC levels measured by P-MRS were similar in MDAMB-231 cells (human breast carcinoma) treated by an anticancer drug and thereby concluded that the decrease in tCho peak was mainly due to the drop in PC, as major component of the tCho peak [6]. Ultimately, we share the opinion that further experimental/pre-clinical studies comparing different choline imaging techniques in a synergistic way are mandatory to fully elucidate the complexity of the Kennedy pathway.

Early monitoring of external radiation therapy by [18F]-fluoromethylcholine positron emission tomography and 3-T proton magnetic resonance spectroscopy: an experimental study in a rodent rhabdomyosarcoma model

To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in (18)F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model. Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT. Total choline concentration was expressed in arbitrary units as the area under the curve of the 3.2-ppm peak on H-MR spectra. FCH uptake was expressed as maximum standardized uptake value (SUV(max)) and as the % of injected dose per gram (%ID/g) after precise tumour delineation on hybrid PET-MR images. Pre- and post-RT data were compared using the Student's paired t test, and results were expressed as mean+/-S.D. Seventeen tumours were available for analysis. A mean drop in choline concentration of 45% was observed 3 days after irradiation (P<.001), whereas a concomitant mean increase in SUV(max) of 41% was observed (P=.006). Choline concentration reincreased on later time points. Opposite trend between increased FCH uptake and decreased tCho peak was observed at 3 days. Later (9 and 16 days), uptake remained stable and tCho peak reincreased.

In Vivo Proton MR Spectroscopy of the Breast Using the Total Choline Peak Integral as a Marker of Malignancy

The purpose of our study was to use the total choline-containing compound (tCho) peak integral as a marker of malignancy in breast MR spectroscopy (MRS). Forty-eight single-voxel water- and fat-suppressed 1.5-T MRS measurements were performed in 42 patients, obtaining both absolute tCho peak integral and tCho peak integral normalized for the volume of interest (VOI). Our reference standard was histology for lesions with BI-RADS category 4 and 5 and histology or at least a 2-year follow-up for findings with BI-RADS 2 and 3 and normal glands. Receiver operating characteristic (ROC) analysis, Mann-Whitney U test, and Spearman's rank correlation were used. Three of 48 measurements (6%) failed. Of the remaining 45 spectra, 18 nonmalignant tissues showed no tCho peak, eight nonmalignant tissues showed a tCho peak integral from 0.99 to 9.03 arbitrary units (AU), and 19 malignant lesions showed a tCho peak integral from 1.26 to 19.80 AU. The diameter of nonmalignant tissues was 16.9 +/- 7.4 mm; that of malignant lesions was 15.3 +/- 6.9 mm (p = 0.308). At ROC analysis, the optimal threshold was 1.90 AU for absolute tCho peak, with 0.895 (17/19) sensitivity, 0.923 (24/26) specificity, and an AUC (area under the curve) of 0.917 (95% CI, 0.822-1.000); the optimal threshold was 0.85 AU/mL for the normalized tCho peak integral with 0.842 (16/19) sensitivity, 0.885 (23/26) specificity, and an AUC of 0.941 (0.879-1.000) (p = 0.470). A negative correlation (p = 0.011) was found between the VOI and the normalized tCho peak integral of malignant tissues. Breast MRS using tCho peak integral reaches a high level of diagnostic performance.

1H HR‐MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas

We investigate the profile of choline metabolites and the expression of the genes of the Kennedy pathway in biopsies of human gliomas (n = 23) using (1)H High Resolution Magic Angle Spinning (HR-MAS, 11.7 Tesla, 277 K, 4000 Hz) and individual genetic assays. (1)H HR-MAS spectra allowed the resolution and relative quantification by the LCModel of the resonances from choline (Cho), phosphocholine (PC) and glycerophosphorylcholine (GPC), the three main components of the combined tCho peak observed in gliomas by in vivo (1)H NMR spectroscopy. All glioma biopsies depicted a prominent tCho peak. However, the relative contributions of Cho, PC, and GPC to tCho were different for low and high grade gliomas. Whereas GPC is the main component in low grade gliomas, the high grade gliomas show a dominant contribution of PC. This circumstance allowed the discrimination of high and low grade gliomas by (1)H HR-MAS, a result that could not be obtained using the tCho/Cr ratio commonly used by in vivo (1)H NMR spectroscopy. The expression of the genes involved in choline metabolism has been investigated in the same biopsies. High grade gliomas depict an upregulation of the beta gene of choline kinase and phospholipase C, as well as a downregulation of the cytidyltransferase B gene, the balance of these being consistent with the accumulation of PC. In the low grade gliomas, phospholipase A(1) and lysophospholipase are upregulated and phospholipase D is downregulated, supporting the accumulation of GPC. The present findings offer a promising procedure that will potentially help to accurately grade glioma tumors using (1)H HR-MAS, providing in addition the genetic background for the alterations of choline metabolism observed in high and low grade gliomas.

Diagnosis of intraductal pathology by breast duct micro-endoscopy (BDME)

To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV 1H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes.A prospective study of SV 1H MRS was performed following dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in 61 women using a 3 T MR system. All lesions (n = 57) were analysed for characteristics of morphology, contrast-enhancement kinetics, and tCho peak heights at SV 1H MRS that were two-times above baseline. Subsequently, the tCho in selected lesions (n = 32) was quantified by calculating the area under the curve, and a tCho concentration equal to or greater than the cut-off value was considered to represent malignancy. The relationship between tCho in invasive ductal carcinomas (IDCs) and their Bloom & Richardson grading of malignancy was assessed.Fifty-two patients (57 lesions; 42 malignant and 15 benign) were analysed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), of predicting malignancy were 100, 73.3, 91.3, and 100%, respectively, using DCE-MRI and 95.2, 93.3, 97.6, and 87.5%, respectively, using SV 1H MRS. The tCho cut-off for receiver operating characteristic (ROC) curve was 0.33 mmol/l. The relationship between tCho levels in malignant breast lesions with their histopathological subtypes was not statistically significant (p = 0.3).Good correlation between tCho peaks and malignancy, enables SV 1H MRS to be used as a clinically applicable, simple, yet non-invasive tool for improved specificity and diagnostic accuracy in detecting breast cancer.

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

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.