Point-resolved Spectroscopic Sequence Research Articles

2-Hydroxyglutarate magnetic resonance spectroscopy in adult brainstem glioma.

Adult brainstem gliomas (BSGs) are rare tumors of the CNS that are poorly understood. Upregulation of the oncometabolite 2-hydroxyglutarate (2HG) in the tumor indicates the mutation of isocitrate dehydrogenase (IDH), which can be detected by magnetic resonance spectroscopy (MRS). Although histological examination is required for the definitive diagnosis of BSG, 2HG-optimized MRS (2HG-MRS) may be useful, considering the difficult nature of brainstem lesion biopsy. The aim of this study was to evaluate the utility of 2HG-MRS for diagnosing IDH-mutant adult BSG. Patients with a radiographically confirmed brainstem tumor underwent 3T MRS. A single voxel was set in the lesion with reference to the T2 or fluid-attenuated inversion recovery image and analyzed according to the 2HG-tailored MRS protocol (point-resolved spectroscopic sequence; echo time 35 msec). All patients underwent intraoperative navigation-guided or CT-guided stereotactic biopsy for histopathological diagnosis. The status of IDH and H3K27M mutations was confirmed by immunohistochemistry and direct DNA sequencing. In addition, the authors examined the relationship between patients' 2HG concentrations and survival time. Ten patients (7 men, 3 women; median age 33.5 years) underwent 2HG-MRS and biopsy. Four patients had an H3K27M mutation and 4 had an IDH1 mutation (1 R132H canonical IDH mutation, 2 R132S and 1 R132G noncanonical IDH mutations). Two had neither H3K27M nor IDH mutations. The H3K27M and IDH mutations were mutually exclusive. Most tumors were located in the pons. There was no significant radiological difference between mutant H3K27M and IDH on a conventional MRI sequence. A 2HG concentration ≥ 1.8 mM on MRS demonstrated 100% (95% CI 28%-100%) sensitivity and 100% (95% CI 42%-100%) specificity for IDH-mutant BSG (p = 0.0048). The median overall survival was 10 months in IDH-wild-type BSG patients (n = 6) and could not be estimated in IDH-mutant BSG patients (n = 4) due to the small number of deaths (p = 0.008). 2HG-MRS demonstrated high sensitivity and specificity for the prediction of IDH-mutant BSG. In addition, 2HG-MRS may be useful for predicting the prognosis of adult BSG patients.

Glutamic Acid and Total Creatine as Predictive Markers for Epilepsy in Glioblastoma by Using Magnetic Resonance Spectroscopy Before Surgery

Epilepsy in glioblastoma patients significantly reduces their quality of life; however, little is known about the association between predicting epilepsy and metabolites in tumors. In this study, we used 3.0-T magnetic resonance imaging and 1H-magnetic resonance spectroscopy (MRS) to quantify metabolite concentrations in patients with varying epilepsy histories. Fifty-one patients with glioblastoma underwent pretreatment 3.0-T MRI/1H-MRS scanning. Single-voxel (1.5 cm3) MRS, in an enhanced lesion, was acquired using adouble-echo point-resolved spectroscopic sequence with chemical-shift selective water suppression. MRS data were quantified with linear combination model (LC-Model) software. We compared the MRS data between groups withand without epilepsy during the postoperative course(EP). The ratios of glutamate (Glu) and glutamate+ glutamine (Glx) to total creatine (Glu/tCr and Glx/tCr) in the tumor were associated with epilepsy history. The receiver operating characteristic curve analysis showed that a Glu/tCr value of 1.81 was 70% sensitive and 90% specific for the prediction of EP (area under curve: 0.82). In the analysis excluding patients with preoperative epilepsy, a Glu/tCr value of 1.81 was 75% sensitive and 88% specific for the prediction (area under curve: 0.87). Intratumoral metabolite concentrations measured using pretreatment 3.0-T MRI/1H-MRS changed characteristically in the group with EP. Our study suggests that the Glu/tCr ratio in tumors has adequate reliability in predicting EP. Pretreatment MRS is a minimally invasive and simple procedure that can provide useful information on glioblastoma patients.

Reliability of Glutamate Quantification in Human Nucleus Accumbens Using Proton Magnetic Resonance Spectroscopy at a 70-cm Wide-Bore Clinical 3T MRI System.

The human nucleus accumbens is a challenging region to study using proton magnetic resonance spectroscopy (1H-MRS) on a 70-cm wide-bore clinical 3T MRI system. The aim of this study was to investigate the reliability for quantitative measurement of glutamate concentration in the nucleus accumbens using a 70-cm wide-bore clinical 3T MRI. 1H-MRS of the nucleus accumbens was acquired using the Point-Resolved Spectroscopic Sequence (PRESS) with echo time of 40 ms from 10 healthy volunteers (5 female; age range: 18–30 years) on two separate visits (a baseline, and 1-month time point). The Java-based Magnetic Resonance User Interface (jMRUI) software package was used to quantitatively measure the absolute metabolite concentrations. The test-retest reliability and reproducibility were assessed using intraclass correlations coefficients (ICC), and coefficients of variation (CV). Glutamate concentrations were similar across visits (P = 0.832). Reproducibility measures for all metabolites were good with CV ranging from 7.8 to 14.0%. The ICC values of all metabolites for the intra-class measures were excellent (ICC > 0.8), except that the reliability for Glx (glutamate + glutamine) was good (ICC = 0.768). Pearson correlations for all metabolites were all highly significant (r = 0.636–0.788, P < 0.05). In conclusion, the short-echo-time PRESS can reliably obtain high quality glutamate spectrum from a ~3.4 cm3 voxel of the nucleus accumbens using a 70-cm wide-bore clinical 3T MRI.

Feasibility ofIn vivoProton Magnetic Resonance Spectroscopy for Lung Cancer

Purpose : To investigate the feasibility of in vivo proton magnetic resonance spectroscopy (MRS) for evaluation of lung cancer. Materials and Methods: This prospective study was approved by the institutional review board of our hospital and informed consent was obtained in all patients. Ten patients (7 men, 3 women; mean age, 64.4) with pathologicallyproven lung cancer (mean, 56.8 mm; range, 44-77 mm) were enrolled to 1.5 T MRS using a single-voxel respiration-triggered point-resolved spectroscopic sequence. Technical success rate and the reason of technical failure, if any, were investigated. Results: Out of 10 lung cancers, analyzable MRS spectra were obtained in 8 tumors (technical success rate, 80%). Two MRS datasets were not able to be analyzed due to serious baseline distortion. Choline and lipid signals were detected as major metabolites in analyzable MRS spectra. Conclusion: In vivo proton MRS method using a single-voxel respiration-triggered point-resolved spectroscopic sequence is feasible in obtaining the MR spectra of lung cancer because these spectra were analyzable and high success rate was shown in our study although there was the limitation of small patient group.

Three-dimensional Proton MR Spectroscopic Imaging at 3 T for the Differentiation of Benign and Malignant Breast Lesions

To evaluate the diagnostic accuracy of quantitative, three-dimensional (3D) magnetic resonance (MR) spectroscopic imaging at 3 T for the differentiation of benign and malignant breast lesions, on the basis of choline (Cho) signal-to-noise ratio (SNR) threshold levels, in a clinically feasible measurement time. Institutional review board approval and written informed consent were obtained from all subjects. Fifty female patients (mean age, 50 years; age range, 25-82 years) with mammographic or ultrasonographic (US) abnormalities were successfully examined in the prone position with a 3-T MR system by using a dedicated breast coil. Lesions were verified by either histopathologic examination or follow-up of at least 24 months. For 3D MR spectroscopic imaging, a point-resolved spectroscopic sequence (repetition time msec/echo time msec, 750/145; field of view, 12 × 12 × 12 cm(3); matrix size, 12 × 12 × 12, interpolated to 16 × 16 × 16; acquisition time, 11 minutes 17 seconds) was used. The maximum Cho SNR was assessed in all lesions and correlated with the histopathologic results. Thirty-two malignant and 12 benign lesions were confirmed in 43 patients with histopathologic examination. Seven patients without biopsy underwent imaging follow-up. In 31 of 32 (97%) malignant and 10 of 19 (53%) benign lesions, Cho was detected. The median Cho SNR in malignant lesions was 5.7, compared with 2.0 in benign lesions. With a Cho SNR threshold level of 2.6, 3D MR spectroscopic imaging provided a sensitivity of 97% and a specificity of 84% for the differentiation of benign and malignant breast lesions. At 3T, 3D MR spectroscopic imaging yields high diagnostic sensitivity and specificity for discrimination of benign and malignant breast lesions within reasonable measurement times. This technique allows the study of heterogeneous and multicentric breast tumors and simplifies acquisition planning.

Hepatic lipid composition analysis using 3.0-T MR spectroscopy in a steatotic rat model

Purpose To investigate the feasibility of in vivo assessment of hepatic lipid composition using 3.0-T proton magnetic resonance spectroscopy ( 1H-MRS) in a steatotic rat model and compare it to histopathological and biochemical assessment. Materials and Methods Hepatic steatosis was induced by feeding rats with a methionine/choline-deficient (MCD) diet for 1, 2, 3, 5 or 7 weeks ( n=5 per group). At the end of the diet period, 1H-MRS of the liver was performed, and rats were sacrificed for histopathological and biochemical assessment of the liver. Spectra were acquired in a single voxel (1.2 cc) using a point-resolved spectroscopic sequence with TE/TR=35/2000 ms and 64 signal acquisitions. From the MR spectra, peak area ratios were calculated to estimate hepatic lipid composition. Results During MCD diet periods, hepatic steatosis significantly increased on histopathology ( P<.001). The 1H-MRS measurements of total hepatic fat content [1.3/(1.3+4.65) ppm] correlated strongly with histological macrovesicular hepatic steatosis ( r=0.93, P<.001) and with the biochemical total hepatic fatty acids ( r=0.94, P<.001). Total unsaturated fatty acids [TUFA, 5.4/(1.3+4.65) ppm] estimated with 1H-MRS strongly correlated with the biochemical unsaturated fatty acids ( r=0.90, P<.001). Polyunsaturated fatty acids [PUFA, 2.8/(1.3+4.65) ppm] estimated with 1H-MRS strongly correlated with biochemical PUFA ( r=0.91, P<.001). The proportion of total unsaturated fatty acids relative to the amount of total fatty acids (rTUFA, 5.4/1.3ppm) measured with 1H-MRS strongly correlated with the biochemical amount of unsaturated relative to total hepatic fatty acids ( r=0.81, P<.001). The proportion of PUFA relative to the amount of total fatty acids (rPUFA, 2.8/1.3 ppm) measured with 1H-MRS correlated with the biochemical amount of PUFA relative to total fatty acids ( r=0.59, P=0.005,) and with the biochemical amount of omega-6 PUFA relative to total fatty acids ( r=0.73, P<.001). PUFA at 1H-MRS correlated with the histopathologically assessed degree of lobular inflammation in the liver ( r=0.57, P=.001). Conclusion 3.0T 1H-MRS is able to measure poly- and unsaturated hepatic fatty acids and this strongly correlates with biochemical assessment. This study provides evidence that 3.0-T 1H-MRS is a noninvasive technique to assess hepatic lipid composition.

In vivo MRS study of intraventricular tumors

To evaluate the role of MR spectroscopy (MRS) as a noninvasive tool for characterization of intraventricular brain tumors. Twenty-three intraventricular tumors, all histologically classified (11 central neurocytomas [CNC], 5 meningiomas [Men], other intraventricular tumors [OIV], including 2 anaplastic gliomas [WHO III], 1 tumor each of rhabdoid tumor, glioneuronal hamartoma, GBM, hemangiopericytoma, and subependymoma II), were studied by MRS before surgery using a point-resolved spectroscopic sequence (PRESS). Statistically significant differences (P < 0.03) were observed for NAA/Cr and Cho/Cr between CNCs and OIV. A significant difference (P < 0.01) was observed in the presence of Gly between the CNCs and meningiomas, and CNCs and OIV. In addition, the presence of Ala was also significantly different (P < 0.01) between OIV and meningiomas, and OIV and CNCs. The present study has shown that MRS can be useful in characterizing intraventricular tumor and distinguishing CNCs from meningiomas and other intraventricular tumors. Prior information about intraventricular tumor types could be useful to clinicians in planning treatment and resection strategy.

Improved spatial coverage for brain 3D PRESS MRSI by automatic placement of outer‐volume suppression saturation bands

To develop a technique for optimizing coverage of brain 3D (1) H magnetic resonance spectroscopic imaging (MRSI) by automatic placement of outer-volume suppression (OVS) saturation bands (sat bands) and to compare the performance for point-resolved spectroscopic sequence (PRESS) MRSI protocols with manual and automatic placement of sat bands. The automated OVS procedure includes the acquisition of anatomic images from the head, obtaining brain and lipid tissue maps, calculating optimal sat band placement, and then using those optimized parameters during the MRSI acquisition. The data were analyzed to quantify brain coverage volume and data quality. 3D PRESS MRSI data were acquired from three healthy volunteers and 29 patients using protocols that included either manual or automatic sat band placement. On average, the automatic sat band placement allowed the acquisition of PRESS MRSI data from 2.7 times larger brain volumes than the conventional method while maintaining data quality. The technique developed helps solve two of the most significant problems with brain PRESS MRSI acquisitions: limited brain coverage and difficulty in prescription. This new method will facilitate routine clinical brain 3D MRSI exams and will be important for performing serial evaluation of response to therapy in patients with brain tumors and other neurological diseases.

Prospective motion correction for magnetic resonance spectroscopy using single camera retro‐grate reflector optical tracking

To introduce and evaluate a method of prospective motion correction for localized proton magnetic resonance spectroscopy (1H-MRS) using a single-camera optical tracking system. Five healthy participants were scanned at 3T using a point-resolved spectroscopic sequence (PRESS) with a motion-tracking module and phase navigator. Head motion in six degrees was tracked with a Retro-Grate Reflector (RGR) tracking system and target via a mirror mounted inside the bore. Participants performed a series of three predetermined motion patterns during scanning. Left-right rotation (Rz) (average 12°) resulted in an increase in the total choline to total creatine ratio (Cho/Cr) of +14.6 ± 1.5% (P = 0.0009) for scans without correction, but no change for scans with correction (+1.1 ± 1.5%; P = 0.76). Spectra with uncorrected Z-translations showed large lipid peaks (skull) with changes in Cho/Cr of -13.2 ± 1.6% (P = 0.02, no motion correction) and -2.2 ± 2.4% (P = 0.51) with correction enabled. There were no significant changes in the ratios of N-acetylaspartate, glutamate+glutamine, or myo-inositol to creatine compared to baseline scans for all experiments. Prospective motion correction for 1H-MRS, using single-camera RGR tracking, can reduce spectral artifacts and quantitation errors in Cho/Cr ratios due to head motion and promises improved spectral quality and reproducibility.

Detection of prostate cancer: Utility of diffusion-weighted MR imaging and 3D MR spectroscopic imaging

PurposeTo prospectively compare the mean ADC generated from DWI, the mean choline+creatine/citrate ratio generated from 3D MRS and the combined mean ADC and mean choline+creatine/citrate ratio in the detection of prostate cancer, and to correlate between the choline+creatine/citrate ratio and the aggressiveness of malignancy determined by Gleason score, with histopathological examination of the excised gland as the reference standard. Patients and methodsForty-six patients with biopsy-proved cancer underwent pre-operative MRI at 1.5T. Axial T1, axial, coronal and sagittal T2-weighted, diffusion-weighted and 3D MRS using a point-resolved spectroscopic sequence (PRESS) were acquired. The mean ADC, mean choline+creatine/citrate ratio and combined parameters for malignant lesions are correlated with the pathological results. For each malignant lesion choline+creatine/citrate ratio was correlated with the aggressiveness of malignancy determined by Gleason score. Receiver operating characteristic (ROC) curves were used to determine sensitivity, and specificity of the studied parameters, and Kappa measures of agreement were calculated for prostate cancer detection. ResultsThe mean ADC for tumor tissue was 1.0±0.22×10−3mm2/s (mean±SD), and was significantly lower than that for non-tumor tissue 1.44±0.28×10−3mm2/s (p<0.001). For MRS study the mean (choline+creatine)/citrate ratio in tumor tissue was 1.98±1.0, and was significantly higher than that for non-tumor tissue, 0.72±0.39 (p<0.001). By combining both ADC values and (choline+creatine)/citrate ratio for differentiating malignant from non-malignant tissues a receiver operating characteristic analysis (ROC) curve showed Area under curve (AUC=0.93) and was significantly higher than either (choline+creatine)/citrate ratio alone (AUC=0.86) (p<0.001) or ADC value alone (AUC=0.89) (p<0.001). There is an increasing (choline+creatine)/citrate ratio with increasing Gleason score, however, there is overlap between groups. A greater sensitivity of MRS for tumor detection 85% and 92% was present for tumors with Gleason score 4+3 and ⩾4+4, respectively, while for tumors with Gleason score 3+3 the sensitivity was 63%. ConclusionThe combination of ADC and (choline+creatine)/citrate ratio is better than each parameter alone in differentiating between tumor and non-tumor prostatic tissue, also MR spectroscopic imaging findings of prostate tumor (Cho+Cr)/Cit ratio correlate with pathologic Gleason score. The combined parameters offer a promising non-invasive method for the diagnostic workup of prostate cancer.

Elimination of spatial interference in PRESS‐localized editing spectroscopy

Unambiguous detection of gamma-amino butyric acid (GABA) in the human brain is hindered by low concentration and spectral overlap with other metabolites. The popular MEGA-PRESS (PRESS: point-resolved spectroscopic sequence) method allows spectral separation of GABA from other metabolites, but suffers from a significant signal-to-noise ratio (SNR) reduction due to the 4-compartment artifact. An alternative PRESS localization technique (PRESS+4) was investigated and compared to MEGA-PRESS using numerical simulations, phantom, and in vivo experiments. It was shown that while the MEGA-PRESS method suffers significant signal loss ( approximately equal 20% for the difference spectrum), GABA signal intensity in PRESS+4 is reduced by only 2% compared to the nonlocalized condition at 4T. The improved method retains important features of the popular MEGA-PRESS such as additional water suppression and macromolecular elimination as demonstrated in human brain experiments. This method is not limited to GABA J-difference editing, but can be applied in any PRESS-based experiments. It should prove particularly useful at higher field, where the 4-compartment artifact is especially detrimental.

In vivo proton magnetic resonance spectroscopic (PMRS) evaluation: Emerging tool to solve the diagnostic dilemma in soft tissue sarcoma management

10020 Objective: Presently grade is the most important factor used to decide the soft tissue sarcoma management. But it is always very difficult to assign a pathologic grade because of discordance rate is 30–40%, even among experienced sarcoma oncopathologists. Again histopathology has the disadvantages of being invasive, subjective and insensitive to tumour heterogeneity. This emphasizes the need for an objective and accurate assessment of histologic type and grade of sarcoma. The aim of this study is to evaluate the correlation of in vivo proton magnetic resonance spectroscopic findings with histopathological features and validate its diagnostic efficacy in management of different types of soft tissue sarcomas. Methods: PMRS Study was performed at 1.5Tesla MRI machine with a surface coil appropriate for the location of the lesions in 25 patients. Single-voxel (SVS) study has been done in 10 cases and chemical shift imaging (CSI) study characterised the heterogeneity of the tumor in 15 cases by using point - resolved spectroscopic sequence (PRESS) with echo time TR=2,000 / TE = 30, 135 &amp; 270 msec. The choline peak, identified at 3.2 ppm in spectra was considered as significant which shows the activity of the tumour. MRS results and histopathologic findings were correlated and P &lt; 0.001, considered being significant. Results: Choline peak was found in 17 out of 17 patients with malignant soft tissue tumours where as three patient with benign and five treated malignant soft tissue tumour patients with no residual disease did not show any choline. In vivo spectroscopy here shows sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each. Conclusion: Choline peak in MRS study can predict the grade, margin status (especially CSI) and tumour activity in recurrent and / or residual soft tissue sarcoma. Most important findings here was that without using any contrast medium in study the choline peak in CSI spectroscopic evaluation could show the tumor activity at the margin of the tumor which is very important point for evaluation of residual or recurrent or completion of the surgical excision of the tumor A major study should be done to validate its efficacy for routine use in oncology. [Table: see text]

Human cervical lymphadenopathy: evaluation with in vivo 1H-MRS at 1.5 T

To evaluate the feasibility of performing in vivo proton magnetic resonance spectroscopy ((1)H-MRS) of cervical lymph nodes, and the clinical usefulness of the technique in the characterization of cervical lymphadenopathy. Cervical lymphadenopathy was examined in 20 individuals with malignant disease, i.e. 10 with squamous cell carcinoma (SCC), 6 with undifferentiated carcinoma (UDC) and 4 with non-Hodgkin's lymphoma (NHL). Cervical lymphadenopathy was also examined in 4 individuals with benign disease, i.e. 3 with tuberculosis (TB) and 1 with Castleman's disease. A point-resolved spectroscopic sequence with echo times (TE) of 136 and 272 ms and a time-domain spectral fitting procedure were used to estimate peak amplitude of choline (Cho), creatine (Cr) and unsuppressed water. Cho/Cr and Cho/water ratios were measured for each lesion. The mean ratio for each lesion group was obtained and results were compared statistically. At TE of 136 ms, spectra were interpretable in all 24 cases and a Cr peak was identified with post-processing in 15 cases. The Cho/Cr and Cho/water ratios for NHL were 9.1 +/- 5.2 and 1.7 +/- 0.2 x 10(-3), for UDC were 4.4 +/- 0.9 and 1.2 +/- 0.4 x 10(-3), and for SCC were 2.1 +/- 0.6 and 0.5 +/- 0.3 x 10(-3), respectively. Both Cho/Cr and Cho/water ratios for UDC were significantly higher than SCC (p = 0.002 and 0.026, respectively). At TE of 272 ms, spectra were interpretable in 22 of 24 cases and a Cr peak was identified with post-processing in 11 cases. Cho/Cr and Cho/water ratios for NHL were 5.4 and 4.6 +/- 1.4 x 10(-3), for UDC were 4.2 +/- 1.5 and 2.6 +/- 1.0 x 10(-3) and for SCC were 2.5 +/- 1.1 and 1.3 +/- 0.6 x 10(-3), respectively. The Cho/water ratio for UDC was significantly higher than for SCC (p = 0.04). The Cho/Cr ratio for UDC was also higher than for SCC, but this difference was not statistically significant (p = 0.07). Neither Cho nor Cr was detected in the 3 cases of TB. In vivo (1)H-MRS is a feasible technique for the evaluation of cervical lymph nodes and it offers potential as a clinical tool in the investigation of cervical lymphadenopathy. However, further studies with larger patient cohorts are needed to validate the findings of this initial report.

Characterization of bone and soft-tissue tumors with in vivo 1H MR spectroscopy: initial results.

To determine if in vivo detection of choline by using hydrogen 1 (1H) magnetic resonance (MR) spectroscopy with dynamic contrast material-enhanced MR imaging can help differentiate between benign and malignant musculoskeletal tumors. MR imaging was performed in 36 consecutive patients with bone and soft-tissue tumors larger than 1.5 cm in diameter. Examinations were performed at 1.5 T with a surface coil appropriate for the location of the lesions. Single-voxel 1H MR spectroscopy was performed by using a point-resolved spectroscopic sequence with echo times of 40, 135, and 270 msec. The volume of interest within lesions was positioned on the areas of early enhancement (<8 seconds after arterial enhancement) according to the findings of dynamic contrast-enhanced MR imaging with subtraction. The criterion for determining whether choline was present in a lesion was a clearly identifiable peak at 3.2 ppm in at least two of the three spectra acquired at echo times. MR spectroscopic results and histopathologic findings were determined in blinded fashion and compared with kappa statistics. P <.001 was considered to indicate a significant difference. Choline was detected in 18 of 19 patients with malignant tumors and in three of 17 patients with benign lesions. The three benign lesions included one perineurioma, one giant cell tumor, and one abscess. Choline was not detected in 14 patients with benign lesions nor in one patient with a densely ossifying low-grade parosteal osteosarcoma. In vivo 1H MR spectroscopy characterized bone and soft-tissue tumors, resulting in a sensitivity of 95%, specificity of 82%, and accuracy of 89% (P <.001). Choline can be reliably detected in large malignant bone and soft-tissue tumors by using a multiecho point-resolved spectroscopic protocol. 1H MR spectroscopy can help differentiate malignant from benign musculoskeletal tumors by revealing the presence or absence of water-soluble choline metabolites.

Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study

Proton magnetic resonance spectroscopy ( 1H-MRS) was used to assess neurochemical brain changes across the menstrual cycle in five women with premenstrual dysphoric disorder (PMDD) and six control subjects. Women with PMDD and control subjects were scanned on days 8 and 26 within one menstrual cycle (i.e. at times of complete absence and height of PMDD symptoms, respectively). The point resolved spectroscopic sequence (PRESS) was used to localize a voxel of 8 ml in the medial frontal gray matter and in the occipito-parietal white matter. The ratio of N-acetyl-aspartate to creatine in the region of the medial prefrontal cortex and the cingulate gyrus declined significantly from the follicular to the luteal phase in both groups of subjects. The menstrual phase-dependent significant increase in the ratio of choline to creatine was observed in the parietal white matter. The myo-inositol/creatine ratio exhibited a trend toward higher levels in the PMDD patients in the luteal phase of the menstrual cycle. Differences between PMDD and control subjects were not statistically significant. Menstrual cycle phase-dependent changes in ovarian hormonal concentrations may influence the neurochemistry of brain activity in premenopausal women.