In vivo assignment of methylmalonic acid in breast tissue using 2D MRS and relationship with breast density, menopausal status and cancer risk.

BACKGROUND: Methylmalonic acid (MMA) is linked to progression and aggressiveness of tumours. A recent study showed that high levels of circulatory MMA directed genetic programs promoting cancer progression. PURPOSE: To evaluate in vivo two-dimensional correlated spectroscopy (2D COSY) data from women at elevated risk of breast cancer to determine if resonances consistent with MMA are present, and if so to correlate levels with breast density, menopausal status and risk categories. MATERIALS AND METHODS: With institutional review board approval, 106 women at elevated risk (mean age 47), including 46 participants at medium risk, 43 at high risk with no known mutation and 17 BRCA-mutation carriers, were recruited. Breast density was assessed using a T2 sequence. A T1 sequence was used to place the voxel for the 2D COSY data. Peak volumes were normalized to the methylene peak at (1.30, 1.30) ppm. Chi-squared and Mann-Whitney tests were used. RESULTS: Two resonances are assigned on the diagonal at 3.15 ppm and 3.19 ppm consistent with and denoted MMA1 and MMA2 respectively. MMA1 and MMA2 increased in parallel with increased risk. BRCA-mutation carriers recorded an increase in mean MMA1 of 120% (p = 0.033) and MMA2 of 127% (p = 0.020) in comparison with participants with no known mutation. BRCA-mutation carriers with dense breasts recorded a significant increase in mean MMA1 of 137% (p = 0.002) and in mean MMA2 of 143% (p = 0.004) compared with BRCA-mutation participants with low-density breast tissue. MMA1 and MMA2 were higher in premenopausal women with dense breasts compared with those with low-density tissue. The highest values of MMA were recorded in BRCA-mutation carriers. CONCLUSION: Two tentative assignments are made for MMA in breast tissue of women at elevated risk for cancer. BRCA-mutation carriers exhibited higher values of MMA than those with no known mutation. Premenopausal women with BRCA mutation and dense breasts recorded the highest levels of MMA compared with other categories.

Two-dimensional correlated spectroscopy records reduced neurotransmission in blast-exposed artillery soldiers after live fire training.

There is a requirement for an objective method to determine a safe level of low-level military occupational blast, having recognised it can lead to neurological damage. The purpose of the current study was to evaluate the effect of artillery firing training on the neurochemistry of frontline soldiers using two-dimensional (2D) COrrelated SpectroscopY (2D COSY) in a 3-T clinical MR scanner. Ten men considered to be of sound health were evaluated before and after a week-long live firing exercise in two ways. Prior to the live fire exercise, all participants were screened by a clinical psychologist using a combination of clinical interviews and psychometric tests, and were then scanned with 3-T MRI. The protocols included T1- and T2-weighted images for diagnostic reporting and anatomical localisation and 2D COSY to record any neurochemical effects from the firing. No changes to the structural MRI were recorded. Nine substantive and statistically significant changes in the neurochemistry were recorded as a consequence of firing training. Glutamine and glutamate, glutathione, and two of the seven fucose-α (1-2)-glycans were significantly increased. N-acetyl aspartate, myo-inositol + creatine, and glycerol were also increased. Significant decreases were recorded for the glutathione cysteine moiety and tentatively assigned glycan with a 1-6 linkage (F2: 4.00, F1: 1.31 ppm). These molecules are part of three neurochemical pathways at the terminus of the neurons providing evidence of early markers of disruption to neurotransmission. Using this technology, the extent of deregulation can now be monitored for each frontline defender on a personalised basis. The capacity to monitor early a disruption in neurotransmitters, using the 2D COSY protocol, can observe the effect of firing and may be used to prevent or limit these events.

Breast Tissue Chemistry Measured In Vivo In Healthy Women Correlate with Breast Density and Breast Cancer Risk.

BACKGROUND: The relationship of tissue chemistry to breast density and cancer risk has not been documented despite breast density being a known risk factor. PURPOSE: To investigate whether distinct chemical profiles associated with breast density and cancer risk are identified in healthy breast tissue using in vivo two-dimensional correlated spectroscopy (2D COSY). STUDY TYPE: Prospective. POPULATION: One-hundred-seven participants including 55 at low risk and 52 at high risk of developing breast cancer. FIELD STRENGTH/SEQUENCE: 3 T/ axial/ T1, T2, 2D COSY. ASSESSMENT: Two radiologists defined breast density on T2. Interobserver variability assessed. Peak volumes normalized to methylene at (1.30, 1.30) ppm as internal shift reference. STATISTICAL TESTS: Chi-squared/Mann-Whitney/Kappa statistics/Kruskal Wallis/pairwise analyses. Significance level 0.05. RESULTS: Ten percentage were fatty breasts, 39% scattered fibroglandular, 35% heterogeneously dense, and 16% extremely dense. Interobserver variability was excellent (kappa = 0.817). Sixty percentage (64/107) were premenopausal. Four distinct tissue chemistry categories were identified: low-density (LD)/premenopausal, high-density (HD)/premenopausal, LD/postmenopausal, and HD/postmenopausal. Compared to LD, HD breast chemistry showed significant increases of cholesterol (235%) and lipid unsaturation (33%). In the low-risk category, postmenopausal women with dense breasts recorded the largest significant changes including cholesterol methyl 540%, lipid unsaturation 207%, glutamine/glutamate 900%, and choline/phosphocholine 800%. In the high-risk cohort, premenopausal women with HD recorded a more active chemical profile with significant increases in choline/phosphocholine 1100%, taurine/glucose 550% and cholesterol sterol 250%. DATA CONCLUSION: Four distinct chemical profiles were identified in healthy breast tissue based on breast density and menopausal status in participants at low and high risk. Gradual increase in neutral lipid content and metabolites was noted in both risk groups across categories in different order. In low risk, the HD postmenopausal category exhibited the highest metabolic activity, while women at high risk exhibited the highest lipid content and metabolic activity in the HD premenopausal category. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Methodological consensus on clinical proton MRS of the brain: Review and recommendations.

Proton MRS (1 H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a consensus is presented on deficiencies in widely available MRS methodology and validated improvements that are currently in routine use at several clinical research institutions. In particular, the localization error for the PRESS localization sequence was found to be unacceptably high at 3 T, and use of the semi-adiabatic localization by adiabatic selective refocusing sequence is a recommended solution. Incorporation of simulated metabolite basis sets into analysis routines is recommended for reliably capturing the full spectral detail available from short TE acquisitions. In addition, the importance of achieving a highly homogenous static magnetic field (B0 ) in the acquisition region is emphasized, and the limitations of current methods and hardware are discussed. Most recommendations require only software improvements, greatly enhancing the capabilities of clinical MRS on existing hardware. Implementation of these recommendations should strengthen current clinical applications and advance progress toward developing and validating new MRS biomarkers for clinical use.

Lipid and Metabolite Deregulation in the Breast Tissue of Women Carrying BRCA1 and BRCA2 Genetic Mutations.

PURPOSE: To use localized correlated spectroscopy (COSY) to assess for an altered biochemical state or states in breast tissue of women with BRCA gene mutations that potentially constitute preinvasive conditions. MATERIALS AND METHODS: Institutional review board approval was obtained. Participants provided written informed consent. In vivo localized COSY images were recorded at 3 T in the breast tissue of women carrying BRCA1 (n = 9) or BRCA2 (n = 14) gene mutations and were compared with images in healthy control subjects with no family history of breast cancer (n = 10). All participants underwent contrast material-enhanced MR imaging and ultrasonography (US). Statistical significance was calculated with the Mann-Whitney two-sided nonparametric test. RESULTS: No abnormality was recorded with MR imaging or US. Metabolite levels in the BRCA1 cohort were reduced by 79% (P = .014) when compared with triglycerides level, and there was a 19% increase in lipid unsaturation and triglyceride levels (P = .027 and P = .086, respectively) when compared with cellular cholesterol level. Cholesterol level was reduced by 47% (P = .027) when compared with diallylic lipid level. Metabolite levels in the BRCA2 cohort showed increased unsaturation of 21% (P = .030) relative to triglycerides level. Comparison of the BRCA1 and BRCA2 cohorts showed a 47% (P = .002) increase in cholesterol level in the BRCA2 cohort when compared with diallylic lipid level and a 52% (P = .003) increase when compared with triglycerides level. Levels of diallylic lipid, unsaturated lipid, triglycerides, and terminal methyl on the acyl chain are reduced by 46% (P = .002), 57% (P = .003), 66% (P = .003), and 29% (P = .010), respectively, when compared with cholesterol level. CONCLUSION: Localized COSY recorded significant changes in women with BRCA1 and BRCA2 gene mutations when compared with control subjects. If these changes are ultimately proven to be a premalignant stage, this method may prove useful in screening.

Six fucose-α(1-2) sugars and α-fucose assigned in the human brain using in vivo two-dimensional MRS.

A growing body of literature has indicated that fucose-α(1-2)-galactose sugars are implicated in the molecular mechanisms that underlie neuronal development, learning and memory in the human brain. An understanding of the in vivo roles played by these terminal fucose residues has been hampered by the lack of technology to non-invasively monitor their levels in the human brain. We have implemented in vivo two-dimensional MRS technology to examine the human brain in a 3-T clinical MR scanner, and report that six fucose-α(1-2)-galactose residues and free α-fucose are available for inspection. Fucose-α(1-3)-galactose residues cannot yet be assigned using this technology as they resonate under the water resonance. This new application offers an unprecedented insight into the molecular mechanisms by which fucosylated sugars contribute to neuronal processes and how they alter during development, ageing and disease.

Clinical proton MR spectroscopy in central nervous system disorders.

A large body of published work shows that proton (hydrogen 1 [(1)H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of (1)H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of (1)H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which (1)H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.

Case Report: Capacity to Objectively Monitor the Response of a Chronic Pain Patient to Treatment.

Response to pain therapy is currently by patient self-report. We demonstrate that by evaluating the neurochemistry of a patient, using two-dimensional Correlated SpectroscopY (2D COSY) in a 3T MRI scanner, response to therapy can be recorded. A chronic temporomandibular joint (TMJ) pain patient was evaluated by a pain physician specializing in temporomandibular disorders (TMD), and by 2D COSY, before, and 6 days after treatment with Botulinum Toxin A. Prior to treatment the self-reported pain score was 8/10 and reduced to 0/10 within 24 h of treatment. The neurochemistry of the patient prior to treatment was typical of chronic pain. In particular, the Fuc-α(1-2) glycans were affected. Following treatment, the substrates, α-L Fucose, were elevated and the Fuc-α(1-2) glycans repopulated. The depletion of the molecule assigned the glutathione cysteine moiety, with chronic pain, is indicative of a Glutathione redox imbalance linked to neurodegeneration. This new approach to monitor pain could help discriminate the relative contributions in the complex interplay of the sensory and affective (emotional suffering) components of pain leading to appropriate individualized pharmaceutical drug regimens.

Two-dimensional correlated spectroscopy distinguishes clear cell renal cell carcinoma from other kidney neoplasms and non-cancer kidney.

Background: Routinely used clinical scanners, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US), are unable to distinguish between aggressive and indolent tumor subtypes in masses localized to the kidney, often leading to surgical overtreatment. The results of the current investigation demonstrate that chemical differences, detected in human kidney biopsies using two-dimensional COrrelated SpectroscopY (2D L-COSY) and evaluated using multivariate statistical analysis, can distinguish these subtypes. Methods: One hundred and twenty-six biopsy samples from patients with a confirmed enhancing kidney mass on abdominal imaging were analyzed as part of the training set. A further forty-three samples were used for model validation. In patients undergoing radical nephrectomy, biopsies of non-cancer kidney cortical tissue were also collected as a non-cancer control group. Spectroscopy data were analyzed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structures with discriminant analysis (OPLS-DA), to identify biomarkers in kidney cancer tissue that was also classified using the gold-standard of histopathology. Results: The data analysis methodology showed good separation between clear cell renal cell carcinoma (ccRCC) versus non-clear cell RCC (non-ccRCC) and non-cancer cortical tissue from the kidneys of tumor-bearing patients. Variable Importance for the Projection (VIP) values, and OPLS-DA loadings plots were used to identify chemical species that correlated significantly with the histopathological classification. Model validation resulted in the correct classification of 37/43 biopsy samples, which included the correct classification of 15/17 ccRCC biopsies, achieving an overall predictive accuracy of 86%, Those chemical markers with a VIP value >1.2 were further analyzed using univariate statistical analysis. A subgroup analysis of 47 tumor tissues arising from T1 tumors revealed distinct separation between ccRCC and non-ccRCC tissues. Conclusions: This study provides metabolic insights that could have future diagnostic and/or clinical value. The results of this work demonstrate a clear separation between clear cell and non-ccRCC and non-cancer kidney tissue from tumor-bearing patients. The clinical translation of these results will now require the development of a one-dimensional (1D) magnetic resonance spectroscopy (MRS) protocol, for the kidney, using an in vivo clinical MRI scanner.

Use of in vivo two-dimensional MR spectroscopy to compare the biochemistry of the human brain to that of glioblastoma.

PURPOSE: To develop an in vivo two-dimensional localized correlation spectroscopy technique with which to monitor the biochemistry of the human brain and the pathologic characteristics of diseases in a clinically applicable time, including ascertainment of appropriate postprocessing parameters with which to allow diagnostic and prognostic molecules to be measured, and to investigate how much of the chemical information, known to be available from malignant cultured cells, could be recorded in vivo from human brain. MATERIALS AND METHODS: The study was approved by the institutional review board and was compliant with HIPAA. With use of a 3.0-T clinical magnetic resonance (MR) unit and a 32-channel head coil, localized correlation spectroscopy was performed in six healthy control subjects and six patients with glioblastoma multiforme (GBM) with an acquisition time of 11 minutes. Two-dimensional spectra were processed and analyzed and peak volume ratios were tabulated. The data used were proved to be normally distributed by passing the Shapiro-Wilk normality test. The first row of the spectra was extracted to examine diagnostic features. The pathologic characteristics and grade of each GBM were determined after biopsy or surgery. Statistically significant differences were assessed by using a t test. RESULTS: The localized correlation spectroscopy method assigned biochemical species from the healthy human brain. The correlation spectra of GBM were of sufficiently high quality that many of the cross peaks, recorded previously from malignant cell models in vitro, were observed, demonstrating a statistically significant difference (P < .05) between the cross peak volumes measured for healthy subjects and those with GBM (which include lipid, alanine, N-acetylaspartate, γ-aminobutyric acid, glutamine and glutamate, glutathione, aspartate, lysine, threonine, total choline, glycerophosphorylcholine, myo-inositol, imidazole, uridine diphosphate glucose, isocitrate, lactate, and fucose). The first row of the spectra was found to contain diagnostic features. CONCLUSION: Localized correlation spectroscopy of the human brain at 3.0 T with use of a 32-channel head coil was performed in 11 minutes and provided information about neurotransmitters, metabolites, lipids, and macromolecules. The method was able to help differentiate healthy brain from the biochemical signature of GBM in vivo. This method may, in the future, reduce the need for biopsy and is now applicable for the study of selected neurologic diseases.

Adiabatic localized correlation spectroscopy (AL-COSY): application in muscle and brain.

PURPOSE: To describe an enhanced version of a localized correlation spectroscopy (L-COSY) by introducing adiabatic radiofrequency (RF) pulses for localization in two dimensions. Adiabatic pulses will improve slice selection profile and reduce chemical shift artifacts. Optimized Mao and adiabatic hyperbolic secant pulses are tested in vivo. MATERIALS AND METHODS: Region of interest is localized by a 90° nonselective adiabatic RF pulse followed by two pairs of adiabatic RF pulses and a terminal 90° RF sinc pulse. Slice profiles for both refocusing pulses and chemical shift artifacts are measured in a water-oil phantom for L-COSY and AL-COSY. In vivo results of both COSY sequences are shown from muscle and brain on a 3 Tesla (T) scanner. RESULTS: Chemical shift artifacts were reduced with AL-COSY compared with L-COSY. Slice profiles of adiabatic pulses were found to be sharper and more symmetrical than those of traditional Mao pulses. One-dimensional (1D) phantom studies showed longer T2 values using AL-COSY sequence. Comparison of 2D spectra obtained revealed spectroscopic peak volume improvements in AL-COSY and less residual water. In vivo 1D comparison showed more inphase and sharper peaks in AL-COSY spectrum. CONCLUSION: The AL-COSY sequence is an improved sequence due to sharper slice selection profiles, reduction of chemical shift artifacts, peak volume improvements in 2D techniques, and less J-modulation.

Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain.

Spinal cord injury (SCI) can be accompanied by chronic pain, the mechanisms for which are poorly understood. Here we report that magnetic resonance spectroscopy measurements from the brain, collected at 3T, and processed using wavelet-based feature extraction and classification algorithms, can identify biochemical changes that distinguish control subjects from subjects with SCI as well as subdividing the SCI group into those with and without chronic pain. The results from control subjects (n=10) were compared to those with SCI (n=10). The SCI cohort was made up of subjects with chronic neuropathic pain (n=5) and those without chronic pain (n=5). The wavelet-based decomposition of frequency domain MRS signals employs statistical significance testing to identify features best suited to discriminate different classes. Moreover, the features benefit from careful attention to the post-processing of the spectroscopy data prior to the comparison of the three cohorts. The spectroscopy data, from the thalamus, best distinguished control subjects without SCI from those with SCI with a sensitivity and specificity of 0.9 (Percentage of Correct Classification). The spectroscopy data obtained from the prefrontal cortex and anterior cingulate cortex both distinguished between SCI subjects with chronic neuropathic pain and those without pain with a sensitivity and specificity of 1.0. In this study, where two underlying mechanisms co-exist (i.e. SCI and pain), the thalamic changes appear to be linked more strongly to SCI, while the anterior cingulate cortex and prefrontal cortex changes appear to be specifically linked to the presence of pain.

Identification of residual breast carcinoma following neoadjuvant chemotherapy: diffusion-weighted imaging--comparison with contrast-enhanced MR imaging and pathologic findings.

PURPOSE: To compare the capability of diffusion-weighted (DW) and contrast material-enhanced magnetic resonance (MR) imaging to provide diagnostic information on residual breast cancers following neoadjuvant chemotherapy and to assess apparent diffusion coefficients (ADCs) of the carcinoma prior to neoadjuvant chemotherapy to determine if the method could help predict response to chemotherapy. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Three hundred ninety-eight patients underwent MR imaging of the breast, including DW MR (b values, 0 and 1500 sec/mm(2)) and contrast-enhanced MR imaging. Of these, the contralateral breast in 73 women was used as a control. Seventy-two patients with 73 lesions with malignant disease were treated by using neoadjuvant chemotherapy and were examined for residual disease following therapy. Three were excluded because of prolonged intervals between final MR imaging and surgery. Thus, 69 patients (70 lesions) with DW and contrast-enhanced MR imaging results were compared with postoperative histopathologic findings. The ADCs of the carcinoma prior to neoadjuvant chemotherapy were calculated for each patient, and those with complete response and residual disease were compared. RESULTS: The accuracy for depicting residual tumor was 96% for DW MR imaging, compared with an accuracy of 89% for contrast-enhanced MR imaging (P = .06). There was no significant difference in prechemotherapy ADCs between pathologic complete response cases and those with residual disease. CONCLUSION: DW MR imaging had at least as good of accuracy as did contrast-enhanced MR imaging for monitoring neoadjuvant chemotherapy. The ADCs prior to chemotherapy did not predict response to chemotherapy. The use of DW imaging to visualize residual breast cancer without the need for contrast medium could be advantageous in women with impaired renal function.

Low-power adiabatic sequences for in vivo localized two-dimensional chemical shift correlated MR spectroscopy.

Novel low-power adiabatic sequences are demonstrated for in vivo localized two-dimensional correlated MR spectroscopy, such as correlated spectroscopy and total correlated spectroscopy. The design is based on three new elements for in vivo two-dimensional MRS: the use of gradient modulated constant adiabaticity GOIA-W(16,4) pulses for (i) localization (correlated spectroscopy and total correlated spectroscopy) and (ii) mixing (total correlated spectroscopy), and (iii) the use of longitudinal mixing (z-filter) for magnetization transfer during total correlated spectroscopy. GOIA-W(16,4) provides accurate signal localization, and more importantly, lowers the SAR for both total correlated spectroscopy mixing and localization. Longitudinal mixing improves considerably (fivefolds) the efficiency of total correlated spectroscopy transfer. These are markedly different from previous 1D editing total correlated spectroscopy sequences using spatially nonselective pulses and transverse mixing. Fully adiabatic (adiabatic mixing with adiabatic localization) and semiadiabatic (adiabatic mixing with nonadiabatic localization) methods for two-dimensional total correlated spectroscopy are compared. Results are presented for simulations, phantoms, and in vivo two-dimensional spectra from healthy volunteers and patients with brain tumors obtained on 3T clinical platforms equipped with standard hardware. To the best of our knowledge, this is the first demonstration of in vivo adiabatic two-dimensional total correlated spectroscopy and fully adiabatic two-dimensional correlated spectroscopy. It is expected that these methodological developments will advance the in vivo applicability of multi(spectrally)dimensional MRS to reliably identify metabolic biomarkers.

Molecular imaging of the breast.

OBJECTIVE: Personalized health care centers around the concept that each tumor and its host environment is unique; optimal treatment and expected response for any given woman presenting with a newly diagnosed breast cancer differ from the care and response of other women. CONCLUSION: As more is understood about the molecular subtypes of breast cancer and as development of targeted therapies progresses, the possibility of earlier treatment response assessment and even improved detection will be realized.

Diffusion-weighted imaging of mucinous carcinoma of the breast: evaluation of apparent diffusion coefficient and signal intensity in correlation with histologic findings.

OBJECTIVE: The purposes of this study were to compare the apparent diffusion coefficient (ADC) of mucinous carcinoma of the breast with that of other breast tumors and to analyze correlations between signal intensity on diffusion-weighted images and the histologic features of mucinous carcinoma. SUBJECTS AND METHODS: Two hundred seventy-six patients with 277 lesions, including 15 mucinous carcinomas (13 pure type, two mixed type), 204 other malignant tumors, and 58 benign lesions, were examined with 1.5-T MRI at b values of 0 and 1,500 s/mm(2). The correlations between cellularity and ADC, homogeneity of signal intensity on diffusion-weighted images, and histopathologic findings were analyzed. The difference was statistically significant (p < 0.05). RESULTS: The mean ADC of mucinous carcinoma (1.8 +/- 0.4 x 10(-3) mm(2)/s) was statistically higher than that of benign lesions (1.3+/- 0.3 x 10(-3) mm(2)/s) and other malignant tumors (0.9 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001). The ADC of pure type mucinous carcinoma (1.8 +/- 0.3 x 10(-3) mm(2)/s) was higher than that of mixed type mucinous carcinoma (1.2 +/- 0.2 x 10(-3) mm(2)/s) (p < 0.001) and other histologic types (p > 0.05). The correlation between mean cellularity and the ADC of mucinous carcinoma was significant (rho(s) = -0.754; p = 0.001). The homogeneity of signal intensity on diffusion-weighted images correlated with the homogeneity of histologic structures of mucinous carcinoma (p < 0.001; kappa = 0.826). CONCLUSION: Mucinous carcinoma can be clearly differentiated from other breast tumors on the basis of ADC. The low signal intensity of mucinous carcinoma on diffusion-weighted images appears to reflect the presence of mucin and low cellularity. High signal intensity on diffusion-weighted images may reflect the presence of fibrovascular bundles, increased cell density, or a combination of these features.

Two New Fucose-α (1-2)-Glycans Assigned In The Healthy Human Brain Taking The Number To Seven.

Fucosylated glycans are involved in the molecular mechanisms that underpin neuronal development, learning and memory. The capacity to study the fucose-α(1-2)-glycan residues noninvasively in the human brain, is integral to understanding their function and deregulation. Five fucose crosspeaks were assigned to fucosylated glycans using in vivo two-dimensional magnetic resonance Correlated SpectroscopY (2D L-COSY) of the brain. Recent improvements encompassed on the 3T Prisma (Siemens, Erlangen) with a 64-channel head and neck coil have allowed two new assignments. These are Fuc VI (F2:4.44, F1:1.37 ppm) and Fuc VII (F2: 4.29, F1:1.36 ppm). The Fuc VI crosspeak, close to the water resonance, is resolved due to decreased T1 noise. Fuc VII crosspeak, located between Fuc I and III, is available for inspection due to increased spectral resolution. Spectra recorded from 33 healthy men and women showed a maximum variation of up to 0.02 ppm in chemical shifts for all crosspeaks.

Author Correction: Post-traumatic stress disorder affects fucose-α(1-2)-glycans in the human brain: preliminary findings of neuro deregulation using in vivo two-dimensional neuro MR spectroscopy.

The original article contained errors in the Fig. 1 caption. The incorrect sentence, "The region highlighted by the white box is expanded in Fig. 3" was corrected to, "The region highlighted by the white box is expanded in Fig. 2." This has been corrected in the HTML and PDF of the article.

Post-traumatic stress disorder affects fucose-α(1-2)-glycans in the human brain: preliminary findings of neuro deregulation using in vivo two-dimensional neuro MR spectroscopy.

Post-traumatic stress disorder (PTSD) is triggered by experiencing terrifying event(s) for which there is currently no objective test for a definitive diagnosis. We report a pilot study where two-dimensional (2D) neuro magnetic resonance spectroscopy (MRS), collected at 3 T in a clinical scanner with a 64-channel head coil, identifies neuro deregulation in the PTSD cohort. The control subjects (n = 10) were compared with PTSD participants with minimal co-morbidities (n = 10). The 2D MRS identified statistically significant increases in the total spectral region containing both free substrate fucose and fucosylated glycans of 31% (P = 0.0013), two of multiple fucosylated glycans (Fuc IV and VI) were elevated by 48% (P = 0.002), and 41% (P = 0.02), respectively, imidazole was increased by 12% (P = 0.002), and lipid saturation was increased by 12.5% (P = 0.009). This is the first evidence of fucosylated glycans, reported in animals to be involved in learning and memory, to be affected in humans with PTSD.