Longitudinal inter‐ and intra‐individual human brain metabolic quantification over 3 years with proton MR spectroscopy at 3 T

The longitudinal repeatability of proton MR spectroscopy (¹H‐MRS) in the healthy human brain at high fields over long periods is not established. Therefore, we assessed the inter‐ and intra‐subject repeatability of ¹H‐MRS in an approach suited for diffuse pathologies in 10 individuals, at 3T, annually for 3 years. Spectra from 480 voxels over 360 cm³ (～30%) of the brain, were individually phased, frequency‐aligned, and summed into one average spectrum. This dramatically increases metabolites' signal‐to‐noise‐ratios while maintaining narrow linewidths that improve quantification precision. The resulting concentrations of the N‐acetylaspartate, creatine, choline, and myo‐inositol are: 8.9 ± 0.8, 5.9 ± 0.6, 1.4 ± 0.1, and 4.5 ± 0.5 mM (mean ± standard‐deviation). the inter‐subject coefficients of variation are 8.7%, 10.2%, 10.7%, and 11.8%; and the longitudinal (intra‐subject) coefficients of variation are lower still: 6.6%, 6.8%, 6.8%, and 10%, much better than the 35%, 44%, 55%, and 62% intra‐voxel coefficients of variation. The biological and nonbiological components of the summed spectra coefficients of variation had similar contributions to the overall variance. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Localized proton MR spectroscopy of citrate in vitro and of the human prostate in vivo at 1.5 T

Citrate is a secretory product of the normal prostate, a lack of citrate in prostate tissue is expected to be pathognomonic for adenocarcinoma. In the present study proton AB-signal characteristics of citrate at low field strength of 1.5 T were investigated by volume selective spectroscopic and theoretical methods. The nonappearance of fast phase modulation of the J-coupled system at low field strength in vivo is verified by measurements of sodium citrate solution. In vivo localized spectroscopy of small volume elements of (2 cm)³ with the double spin-echo method within the prostatic gland provides citrate signal reception even using a Helmholtz coil with 170-mm diameter. Volume selective proton spectra with different echo times are presented which are comparable to spectra acquired by former authors with endorectal coils.     

In vivo proton MR spectroscopy of primary tumours,nodal and recurrent disease of the extracranial head and neck

Benign and malignant neoplasms as well as metastatic lymph nodes of 39 patients were examined using localized single voxel magnetic resonance spectroscopy (MRS) [repetition time (TR) 1500, echo time (TE) 135) at 1.5 T. New techniques with simultaneous correction of motion artefacts during the acquisition, three-dimensional saturation pulses, respiratory triggering and smaller volume of interest (VOI) size, were applied. Ratios of peak areas under the choline (Cho) and creatine (Cr) resonances were estimated in all cases and compared with those from samples of normal tissue. Ninety one spectra were acquired in 39 patients, 63 of which were suitable for further evaluation. The smallest VOI was 0.40 cm³. The Cho/Cr ratios in all malignant neoplasms (mean: 5.2, range: 1.7–17.8) were significantly elevated relative to those in the normal muscle structures (mean: 0.9, range: 0.2–1.4), while those in the benign neoplasms were elevated (mean: 24.4, range: 1.4–59.7) with respect to those in the malignant ones. The average Cho/Cr ratio in the metastatic lymph nodes was significantly higher (mean: 4.8, range: 3.3–5.6) than that for benign lymphoid hyperplasia (mean: 2.2, range: 1.0–3.0). MRS measurements were able to differentiate recurrent disease from post-therapeutic tissue changes in 11 out of 13 patients.     

Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3 T.

The quantification of choline-containing compounds (Cho) in hepatic tumors by (1)H MR spectroscopy (MRS) is of great interest because such compounds have been linked to malignancy. In this study, a practical external phantom replacement method for the absolute quantification of hepatic metabolites is demonstrated. We performed experiments at 3 T using a body coil, and used an external phantom containing choline chloride for calibration. We first tested the quantification strategy to confirm its suitability in vivo using a phantom of known concentration and normal brain tissue. The results obtained after coil loading and T(1) and T(2) effects were corrected for were consistent with the known concentration and previously published values. To demonstrate its feasibility, we applied the technique to liver studies conducted on five normal volunteers and four patients with hepatocellular carcinoma, and one patient (also in the latter group) who had undergone post-transcatheter arterial chemoembolization (TACE). The Cho concentrations in the four patients were estimated to be 3.4, 6.3, 7.4, and 14.0 mM, respectively. These values are substantially higher than those obtained from the healthy volunteers (1.3 +/- 0.9 mM (mean +/- SD)). The results indicate that the proposed method is accurate and requires fewer tedious procedures for MRS; therefore, it may be a promising technique for evaluating response to treatment in liver cancer.     

External standard method for the in vivo quantification of choline-containing compounds in breast tumors by proton MR spectroscopy at 1.5 Tesla.

Quantification of choline-containing compounds observed with (1)H MRS of breast tumors is of interest since such compounds have been linked to malignancy. Experiments were performed at 1.5 T with an external standard containing phosphocholine for calibration. In phantom studies, good precision was achieved after correction for T(1)/T(2) effects. T(2) values for choline were estimated for two breast cancer patients. A choline concentration of 2.0 mM was calculated for a third patient, a result comparable to in vitro findings. Magn Reson Med 46:189-192, 2001.     

Role of MR spectroscopy and diffusion-weighted imaging in diagnosis of orbital masses

Purpose

To assess the value of (MRI), (DWI) and (MRS) in the diagnosis of different orbital masses and differentiation between benign and malignant masses.

Localized proton MR spectroscopy of the brain in children

Small-voxel (3.0–8.0 cm³), magnetic resonance (MR) imaging–guided proton MR spectroscopy was performed in 54 patients (aged 6 days to 19 years) with intracranial masses (n = 16), neurodegenerative disorders (n = 34), and other neurologic diseases (n = 4) and in 23 age-matched control subjects without brain disease. A combined short TE (18 msec) stimulatedecho acquisition mode (STEAM) and long TE (135 and/or 270 msec) spin-echo point-resolved spatially localized spectroscopy (PRESS) protocol, using designed radio-frequency pulses, was performed at 1.5 T. STEAM spectra revealed short T2 and/or strongly coupled metabolites; prominent resonances were obtained from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and total creatine (tCr). Lactate was well resolved with the long TE PRESS sequence. Intracranial tumors were readily differentiated from cerebrospinal fluid (CSF) collections. All tumors showed low NAA, high Cho, and reduced tCr levels. Neurodegenerative disorders showed low or absent NAA levels and enhanced mobile lipid, glutamate and glutamine, and inositol levels, consistent with neuronal loss, gliosis, demyelination, and amino acid neuro-toxicity. Preliminary experience indicates that proton MR spectroscopy can contribute in the evaluation of central nervous system abnormalities of infants and children.     

Proton MR spectroscopy in the breast: Technical innovations and clinical applications

Proton magnetic resonance spectroscopy (MRS) is a promising noninvasive diagnostic technique for investigation of breast cancer metabolism. Spectroscopic imaging data may be obtained following contrast‐enhanced MRI by applying the point‐resolved spectroscopy sequence (PRESS) or the stimulated echo acquisition mode (STEAM) sequence from the MR voxel encompassing the breast lesion. Total choline signal (tCho) measured in vivo using either a qualitative or quantitative approach has been used as a diagnostic test in the workup of malignant breast lesions. In addition to tCho metabolites, other relevant metabolites, including multiple lipids, can be detected and monitored. MRS has been heavily investigated as an adjunct to morphologic and dynamic MRI to improve diagnostic accuracy in breast cancer, obviating unnecessary benign biopsies. Besides its use in the staging of breast cancer, other promising applications have been recently investigated, including the assessment of treatment response and therapy monitoring. This review provides guidance on spectroscopic acquisition and quantification methods and highlights current and evolving clinical applications of proton MRS. Level of Evidence 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019.     

Cross‐sectional and longitudinal reproducibility of rhesus macaque brain metabolites: A proton MR spectroscopy study at 3 T

Non‐human primates are often used as preclinical model systems for (mostly diffuse or multi‐focal) neurological disorders and their experimental treatment. Due to cost considerations, such studies frequently utilize non‐destructive imaging modalities, MRI and proton MR spectroscopy (¹H MRS). Cost may explain why the inter‐ and intra‐animal reproducibility of the ¹H MRS observed brain metabolites, are not reported. To this end, we performed test‐retest three‐dimensional brain ¹H MRS in five healthy rhesus macaques at 3 T. Spectra were acquired from 224 isotropic (0.5 cm)³ = 125 μL voxels, over 28 cm³ (～35%) of the brain, then individually phased, frequency aligned and summed into a spectrum representative of the entire volume of interest. This dramatically increases the metabolites' signal‐to‐noise ratios, while maintaining the (narrow) voxel linewidth. The results show that the average N‐acetylaspartate, creatine, choline, and myo‐inositol concentrations in the macaque brain are: 7.7 ± 0.5, 7.0 ± 0.5, 1.2 ± 0.1 and 4.0 ± 0.6 mM/g wet weight (mean ± standard deviation). Their inter‐animal coefficients of variation (CV) are 4%, 4%, 6%, and 15%; and the longitudinal (intra‐animal) CVs are lower still: 4%, 5%, 5%, and 4%, much better than the 22%, 33%, 36%, and 45% intra‐voxel CVs, demonstrating the advantage of the approach and its utility for preclinical studies of diffuse neurological diseases in rhesus macaques. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Diffusion-weighted imaging and proton MR spectroscopy in the characterization of acute disseminated encephalomyelitis

Introduction Acute disseminated encephalomyelitis (ADEM) is usually a monophasic illness characterized by multiple lesions involving gray and white matter. Quantitative MR techniques were used to characterize and stage these lesions. Methods Eight patients (seven males and one female; mean age 19 years, range 5 to 36 years) were studied using conventional MRI (T2- and T1-weighted and FLAIR sequences), diffusion-weighted imaging (DWI) and proton magnetic resonance spectroscopy (MRS). Apparent diffusion coefficient (ADC) values and MRS ratios were calculated for the lesion and for normal-appearing white matter (NAWM). Three patients were imaged in the acute stage (within 7 days of the onset of neurological symptoms) and five in the subacute stage (after 7 days from the onset of symptoms). Results ADC values in NAWM were in the range 0.7–1.24×10⁻³ mm/s² (mean 0.937 ± 0.17 mm/s²). ADC values of ADEM lesions in the acute stage were in the range 0.37–0.68×10⁻³ mm/s² (mean 0.56 ± 0.16 mm/s²) and 1.01–1.31×10⁻³ mm/s² (mean 1.24 ± 0.13 mm/s²) in the subacute stage. MRS ratios were obtained for all patients. NAA/Cho ratios were in the range 1.1–3.5 (mean 1.93 ± 0.86) in the NAWM. NAA/Cho ratios within ADEM lesions in the acute stage were in the range 0.63–1.48 (mean 1.18 ± 0.48) and 0.29–0.84 (mean 0.49 ± 0.22) in the subacute stage. The ADC values, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the acute and subacute stages (P < 0.001, P < 0.027, P < 0.047, respectively). ADC values were significantly different between lesions in the acute (P < 0.009) and subacute stages (P < 0.005) with NAWM. In addition, NAA/Cho and Cho/Cr ratios were significantly different between lesions in the subacute stage and NAWM (P < 0.006, P < 0.007, respectively). Conclusion ADEM lesions were characterized in the acute stage by restricted diffusion and in the subacute stage by free diffusion and a decrease in NAA/Cho ratios. Restricted diffusion and progressive decrease in NAA/Cho ratios may help in staging the disease.     

正常人脑不同区域^1H磁共振波谱研究

目的：应用１Ｈ磁共振波谱技术研究正常人脑内化合物的含量和分布。材料和方法：应用１．５Ｔ磁共振仪对１８例正常人脑进行１Ｈ波谱测试，测量的感兴趣区包括大脑皮层、白质、丘脑和小脑，所用序列为激励回波探测序列（ｓｔｉｍｕｌａｔｅｄｅｃｈｏａｑｕｉｓｉｔｉｏｎｍｏｄｅ，ＳＴＥＡＭ）。结果：１Ｈ磁共振波谱可以检测出脑内许多化合物，如Ｎ－乙酰门冬氨酸（ＮＡＡ）、含胆碱类化合物（Ｃｈｏ）、肌酸和磷酸肌酸（Ｃｒ＋Ｐｃｒ）、谷氨酸和谷氨酰胺（Ｇｌｕ＋Ｇｌｎ）、脂质、乳酸等。各化合物的浓度在脑的不同区域存在着差异。ＮＡＡ／Ｃｈｏ比值在灰质最高，小脑最低。Ｃｒ／Ｃｈｏ比值在小脑最高、白质最低。设定肌酸的浓度在灰质和小脑为１０ｍｍｏｌ／Ｌ，在白质和丘脑为１１ｍｍｏｌ／Ｌ，计算ＮＡＡ的绝对浓度为１３～２３ｍｍｏｌ／Ｌ，并且灰质的含量高于小脑和丘脑。结论：１Ｈ磁共振波谱技术可无创性检测出脑组织中与能量代谢、氨基酸、脂肪酸及神经递质有关的化合物，并可定量测定，有助于研究生理和疾病时脑生化改变。     

MR imaging and proton spectroscopy of the brain in posttraumatic cortical blindness

Magnetic resonance (MR) imaging and localized proton MR spectroscopy of the occipital lobes were performed in a patient with cortical blindness following brain trauma. Computed tomography (CT) scans and MR images of the visual cortex were normal in the acute stage. Six weeks after the trauma, MR images showed cortical lesions in both occipital lobes, while the spectra showed elevated lactate and decreased N-acetyl aspartate levels relative to those of healthy volunteers. One year later, visual acuity had improved and follow-up studies revealed an increase in the ratios of N-acetyl aspartate to choline and creatine. These results demonstrate that parenchymal lesions may develop in brain regions that appear normal at CT and MR imaging during the acute stage after trauma. Metabolic changes can be observed in these areas by means of localized proton MR spectroscopy.     

Quantitative brain proton MR spectroscopy based on measurement of the relaxation time T1 of water

PURPOSE: To provide a straightforward method for metabolite quantitation in the brain. Tissue water concentration can be determined in a voxel by measuring T(1) and it may provide an internal reference for the calculation of the metabolite concentrations. MATERIALS AND METHODS: Water-suppressed stimulated echo acquisition mode spectra were obtained at 1.5T, and the tissue water content was calculated from T(1). RESULTS: The calculated water content values demonstrated very good agreement with literature data. Metabolite concentrations (mmol/liter) in the gray and white matter: N-acetyl-aspartate = 14.02 +/- 1.93, creatine = 9.98 +/- 1.03, and choline = 1.14 +/- 0.24; N-acetyl-aspartate = 11.08 +/- 2.24, creatine = 7.83 +/- 0.66, and choline = 2.05 +/- 0.38, respectively. CONCLUSION: The water content calculated from T(1) can yield an internal reference in MR spectroscopy, and the accurate measurement of metabolite concentrations is feasible. The proposed method is simple and can readily be applied in any MR center without the need for complicated corrections or calibration procedures.     

Interaction of gadolinium‐based MR contrast agents with choline: Implications for MR spectroscopy (MRS) of the breast

It has been shown that magnetic resonance spectroscopy (MRS) can improve the specificity of the MR examination by the spectroscopic detection of choline (Cho). Commonly, the lesion is first visualized on postcontrast studies, and the MRS voxel is prescribed accordingly. The implicit assumption made in this approach is that the presence of gadolinium‐based contrast agents will have a negligible effect on the MR spectra obtained from the lesion. In this work, we examined this assumption by determining the effects of six gadolinium‐based contrast agents: Magnevist, Multihance, Omniscan, Optimark, ProHance, and Dotarem, on the Cho peak in phantoms and in a rat model for breast cancer. We found that only the three negatively‐charged chelates: Magnevist, MultiHance, and Dotarem, broadened the Cho peak in phantoms and reduced the area of the Cho peak in vivo by an average of about 40%. The use of negatively‐charged chelates may lead to an underestimation of the levels of Cho present in human breast cancers, since most studies use MRS postcontrast administration. Therefore, we recommend the use of the neutral chelates in MRI/MRS studies of the breast. Magn Reson Med 2009 © 2009 Wiley‐Liss, Inc.     

Investigation of lipid composition of dissected sentinel lymph nodes of breast cancer patients by 7T proton MR spectroscopy

Purpose:

To determine lipid composition of excised healthy and metastatic sentinel lymph nodes of breast cancer patients, as lipids are a potential discriminatory marker for malignancy.

Materials and Methods:

Ten breast cancer patients undergoing surgical nodal staging were included. ¹H‐magnetic resonance spectroscopic images (MRSI) were acquired without water and lipid suppression (resolution 3.0 × 3.0 × 5.0 mm³). MRSI was compared to histopathology. Six groups of lipid resonances (5.4–5.2, 4.3–4.1, 2.8, 2.3–2.0, 1.6–1.3, 0.9 ppm) were identified. The intensity ratios of the total of these resonances to this total including the water resonance and of each lipid resonance to the total of all lipid resonances were determined. For statistical analysis, a mixed model was applied after logistic transformation. The results were expressed as ratios of the median values of these lipid compositions in metastatic to benign nodes.

Results:

In all, 6/32 (19%) of the excised nodes contained metastases. The ratios of the lipid resonances 5.4–5.2, 4.3–4.1, 2.8, 2.3–2.0, 1.6–1.3, 0.9 ppm between metastatic vs. benign were 0.3, 1.2, 0.2, 0.2, 1.2, and 0.9, respectively. Only the ratios of signals from unsaturated fatty acids to the total lipid signal differed significantly.

Conclusion:

Metastatic axillary lymph nodes contained fewer unsaturated fatty acids than benign nodes. 7T ¹H‐MRS may be useful for detecting axillary breast cancer metastases. J. Magn. Reson. Imaging 2012;387‐392. © 2011 Wiley Periodicals, Inc.     

3D -FLASH序列动态MR增强扫描技术在乳腺疾病中的应用

目的 探讨3D-FLASH动态增强扫描在乳腺疾病检查中的应用价值. 方法 将108例经病理证实的乳腺疾病患者作为研究对象,均为女性,年龄35～76岁,平均47岁,使用Siemens 1.0T超导磁共振扫描仪和双环极阵列乳腺线圈.均先常规平扫,静脉注射造影剂Gd-DTPA(0.1 mmol/kg体重)后,三维-快速小角度激发(3D-FLASH)序列获得双侧乳腺轴位动态增强图像并进行减影. 结果 108例中,良性病变62例,乳腺癌46例,术前MRI诊断符合率81.5%. 结论 3D-FLASH序列动态增强是乳腺病变中最有价值的检查序列.     

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

Purpose:

To quantitatively measure tCho levels in healthy breasts using Proton‐Echo‐Planar‐Spectroscopic‐Imaging (PEPSI).

Materials and Methods:

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).

Results:

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.

Conclusion:

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. J. Magn. Reson. Imaging 2012;36:1113–1123. © 2012 Wiley Periodicals, Inc.     

Magnetic resonance (MR) differential diagnosis of breast tumors using apparent diffusion coefficient (ADC) on 1.5‐T

To review the published reports concerning the apparent diffusion coefficient (ADC) value evaluation for the differentiation between malignant and benign breast tumors, articles were searched with the inclusion criteria: (a) a 1.5‐T unit was used; (b) the diagnostic criteria were clearly stated; (c) diffusion‐weighted images (DWIs) were obtained, and ADC value was calculated; (d) ADC values of breast tumors were reported with mean ± standard deviation (SD). Meta‐analysis from 12 articles revealed that the pooled sensitivity and specificity were 0.89 (95% confidence interval [CI], 0.85–0.91) and 0.77 (95% CI, 0.69–0.84), respectively, and that only the maximum b factor correlated with the mean ADC values of malignant and benign tumors, and the noncancerous breast tissue (P< 0.05,P < 0.01,P< 0.05, respectively). In conclusion, ADC evaluation is useful for the differentiation between malignant and benign breast tumors. J. Magn. Reson. Imaging 2009;30:249–255. © 2009 Wiley‐Liss, Inc.