Diffusion-weighted MR spectroscopy of the prostate.

PURPOSE: Prostate tissue has a complex microstructure, mainly composed of epithelial and stromal cells, and of extracellular (acinar-luminal) spaces. Diffusion-weighted MR spectroscopy (DW-MRS) is ideally suited to explore complex microstructure in vivo with metabolites selectively distributed in different subspaces. To date, this technique has been applied to brain and muscle. This study presents the development and pioneering utilization of 1H-DW-MRS in the prostate, accompanied by in vitro studies to support interpretations of in vivo findings. METHODS: Nine healthy volunteers underwent a prostate MR examination (mean age, 56 years; range, 31-66). Metabolic complexation was studied in vitro using solutions with major compounds found in prostatic fluid of the lumen. DW-MRS was performed at 3 T with a non-water-suppressed single-voxel sequence with metabolite-cycling to concurrently measure metabolite and water signals. The water signal was used in postprocessing as a reference in a motion-compensation scheme. The spectra were fitted simultaneously in the spectral and diffusion-weighting dimensions. Apparent diffusion coefficients (ADCs) were derived by fitting signal decays that were assumed to be mono-exponential for metabolites and biexponential for water. RESULTS: DW-MRS of the prostate revealed relatively low ADCs for Cho and Cr compounds, aligning with their intracellular location and higher ADCs for citrate and spermine supporting their luminal origin. In vitro assessments of the ADCs of citrate and spermine demonstrated their complex formation and protein binding. Tissue concentrations of MRS-detectable metabolites were as expected for the voxel location. CONCLUSIONS: This work successfully demonstrates the feasibility of 1H-DW-MRS of the prostate and its potential for providing valuable microstructural information.

A multivariate curve resolution analysis of multicenter proton spectroscopic imaging of the prostate for cancer localization and assessment of aggressiveness.

In this study, we investigated the potential of the multivariate curve resolution alternating least squares (MCR-ALS) algorithm for analyzing three-dimensional (3D) 1 H-MRSI data of the prostate in prostate cancer (PCa) patients. MCR-ALS generates relative intensities of components representing spectral profiles derived from a large training set of patients, providing an interpretable model. Our objectives were to classify magnetic resonance (MR) spectra, differentiating tumor lesions from benign tissue, and to assess PCa aggressiveness. We included multicenter 3D 1 H-MRSI data from 106 PCa patients across eight centers. The patient cohort was divided into a training set (N = 63) and an independent test set (N = 43). Singular value decomposition determined that MR spectra were optimally represented by five components. The profiles of these components were extracted from the training set by MCR-ALS and assigned to specific tissue types. Using these components, MCR-ALS was applied to the test set for a quantitative analysis to discriminate tumor lesions from benign tissue and to assess tumor aggressiveness. Relative intensity maps of the components were reconstructed and compared with histopathology reports. The quantitative analysis demonstrated a significant separation between tumor and benign voxels (t-test, p < 0.001). This result was achieved including voxels with low-quality MR spectra. A receiver operating characteristic analysis of the relative intensity of the tumor component revealed that low- and high-risk tumor lesions could be distinguished with an area under the curve of 0.88. Maps of this component properly identified the extent of tumor lesions. Our study demonstrated that MCR-ALS analysis of 1 H-MRSI of the prostate can reliably identify tumor lesions and assess their aggressiveness. It handled multicenter data with minimal preprocessing and without using prior knowledge or quality control. These findings indicate that MCR-ALS can serve as an automated tool to assess the presence, extent, and aggressiveness of tumor lesions in the prostate, enhancing diagnostic capabilities and treatment planning of PCa patients.

Metabolic changes assessed by 1H MR spectroscopy in the corpus callosum of post-COVID patients.

OBJECTIVE: Many patients with long COVID experience neurological and psychological symptoms. Signal abnormalities on MR images in the corpus callosum have been reported. Knowledge about the metabolic profile in the splenium of the corpus callosum (CCS) may contribute to a better understanding of the pathophysiology of long COVID. MATERIALS AND METHODS: Eighty-one subjects underwent proton MR spectroscopy examination. The metabolic concentrations of total N-acetylaspartate (NAA), choline-containing compounds (Cho), total creatine (Cr), myo-inositol (mI), and NAA/Cho in the CCS were statistically compared in the group of patients containing 58 subjects with positive IgG COVID-19 antibodies or positive SARS-CoV-2 qPCR test at least two months before the MR and the group of healthy controls containing 23 subjects with negative IgG antibodies. RESULTS: An age-dependent effect of SARS-CoV-2 on Cho concentrations in the CCS has been observed. Considering the subjective threshold of age = 40 years, older patients showed significantly increased Cho concentrations in the CCS than older healthy controls (p = 0.02). NAA, Cr, and mI were unchanged. All metabolite concentrations in the CCS of younger post-COVID-19 patients remained unaffected by SARS-CoV-2. Cho did not show any difference between symptomatic and asymptomatic patients (p = 0.91). DISCUSSION: Our results suggest that SARS-CoV-2 disproportionately increases Cho concentration in the CCS among older post-COVID-19 patients compared to younger ones. The observed changes in Cho may be related to the microstructural reorganization in the CCS also reported in diffusion measurements rather than increased membrane turnover. These changes do not seem to be related to neuropsychological problems of the post-COVID-19 patients. Further metabolic studies are recommended to confirm these observations.

Metabolic alterations in the visual pathway of retinitis pigmentosa rats: A longitudinal multimodal magnetic resonance imaging study with histopathological validation.

Because retinitis pigmentosa (RP) has been shown to cause degenerative changes in the entire visual pathway, there is an urgent need to perform longitudinal assessments of RP-induced degeneration and identify imaging protocols to detect this degeneration as early as possible. In this study, we assessed a transgenic rat model of RP by using complementary noninvasive magnetic resonance imaging techniques, namely, proton magnetic resonance spectroscopy (1 H-MRS), to investigate the metabolic changes in RP. Our study demonstrated decreased concentrations and ratios to creatine (Cr) of N-acetylaspartate (NAA), glutamate (Glu), γ-aminobutyric acid (GABA), and taurine (Tau), whereas myo-inositol (Ins) and choline (Cho) were increased in the visual cortex of Royal College of Surgeons (RCS) rats compared with control rats (p < 0.05). Furthermore, with the progression of RP, the concentrations of NAA, Glu, GABA, and Tau, and the ratios of GABA/Cr and Tau/Cr significantly decreased over time, whereas the concentrations of Ins and Cho and the ratio of Ins/Cr significantly increased over time (p < 0.05). In addition, in RCS rats, NAA/Cr decreased significantly from 3 to 4 months postnatal (p < 0.001), and Cho/Cr increased significantly from 4 to 5 months postnatal (p = 0.005). Meanwhile, the 1 H-MRS indicators in 5-month postnatal RCS rats could be confirmed by immunohistochemical staining. In conclusion, with the progression of RP, the metabolic alterations in the visual cortex indicated progressive reprogramming with the decrease of neurons and axons, accompanied by the proliferation of gliocytes.

Metabolic and physiologic magnetic resonance imaging in distinguishing true progression from pseudoprogression in patients with glioblastoma.

Pseudoprogression (PsP) refers to treatment-related clinico-radiologic changes mimicking true progression (TP) that occurs in patients with glioblastoma (GBM), predominantly within the first 6 months after the completion of surgery and concurrent chemoradiation therapy (CCRT) with temozolomide. Accurate differentiation of TP from PsP is essential for making informed decisions on appropriate therapeutic intervention as well as for prognostication of these patients. Conventional neuroimaging findings are often equivocal in distinguishing between TP and PsP and present a considerable diagnostic dilemma to oncologists and radiologists. These challenges have emphasized the need for developing alternative imaging techniques that may aid in the accurate diagnosis of TP and PsP. In this review, we encapsulate the current state of knowledge in the clinical applications of commonly used metabolic and physiologic magnetic resonance (MR) imaging techniques such as diffusion and perfusion imaging and proton spectroscopy in distinguishing TP from PsP. We also showcase the potential of promising imaging techniques, such as amide proton transfer and amino acid-based positron emission tomography, in providing useful information about the treatment response. Additionally, we highlight the role of "radiomics", which is an emerging field of radiology that has the potential to change the way in which advanced MR techniques are utilized in assessing treatment response in GBM patients. Finally, we present our institutional experiences and discuss future perspectives on the role of multiparametric MR imaging in identifying PsP in GBM patients treated with "standard-of-care" CCRT as well as novel/targeted therapies.

Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of tumor response to nano-photo-thermal therapy.

Nanotechnology-based photothermal therapy (NPTT) is a new emerging modality of cancer therapy. To have the right prediction and early detection of response to NPTT, it is necessary to get rapid feedback from a tumor treated by NPTT procedure and stay informed of what happens in the tumor site. We performed this study to find if proton magnetic resonance spectroscopy (1H-MRS) can be well responsive to such an imperative requirement. We considered various treatment groups including gold nanoparticles (AuNPs), laser, and the combination of AuNPs and laser (NPTT group). Therapeutic effects on CT26 colon tumor-bearing BALB/c mice were studied by looking at alterations that happened in 1H-MRS signals and tumor size after conducting treatment procedures. In MRS studies, the alterations of choline and lipid concentrations and their ratio were investigated. Having normalized the metabolite peak to water peak, we found a significant decrease in choline concentration post-NPTT (from (1.25 ± 0.05) × 10-3 to (0.43 ± 0.04) × 10-3), while the level of lipid concentration in the tumor was slightly increased (from (2.91 ± 0.23) × 10-3 to (3.52 ± 0.31) × 10-3). As a result, the choline/lipid ratio was significantly decreased post-NPTT (from 0.41 ± 0.11 to 0.11 ± 0.02). Such alterations appeared just 1 day after NPTT. Tumor shrinkage in all groups was studied and significant changes were significantly detectable on day 7 post-NPTT procedure. In conclusion, the study of choline/lipid ratio using 1H-MRS may help us estimate what happens in a tumor treated by the NPTT method. Such an in vivo assessment is interestingly feasible as soon as just 1 day post-NPTT. This would undoubtedly help the oncologists make a more precise decision about treatment planning strategies. Monitoring of the choline/lipid ratio by 1H-MRS can be helpful for prediction and early detection of response to nano-photo-thermal therapy.

MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review.

Neuroimaging has been a critical tool for understanding the neuropathological underpinnings observed in HIV. The pathophysiology of HAND is chiefly driven by neuroinflammation. Despite adhering to cART, low levels of viraemia probably persist in the brain in some patients leading to chronic immune activation with resultant neuroinflammation and consequent neuronal injury. MR spectroscopy has been widely used as a biomarker for the presence and severity of HAND in several studies. By studying the MRS signatures, it is possible to characterise the presence of neuroinflammation and neural injury. Furthermore, metabolite concentrations measured by MRS could be used as a quantitative indicator of HIV cerebral involvement, thereby affording the opportunity to assess the efficacy of cART in HAND. However, currently there are three significant limitations in the MRS HIV research literature: the relative paucity of prospective studies, the small number of regions of interrogation due to current methodology (single voxel MRS), and the evolving understanding of the impact of co-morbidities (e.g. ageing, mood disorders, alcoholism etc.) on MRS measurements. This review critically addresses the current literature of MRS studies in people living with HIV (PWH) with HAND to determine its value, especially in the context of the current cART era. In addition, we discuss technical considerations related to the disease and the future direction in HAND using MRS.

Non-water-excitation MR spectroscopy techniques to explore exchanging protons in human brain at 3 T.

PURPOSE: To develop localization sequences for in vivo MR spectroscopy (MRS) on clinical scanners of 3 T to record spectra that are not influenced by magnetization transfer from water. METHODS: Image-selected in vivo spectroscopy (ISIS) localization and chemical-shift-selective excitation (termed I-CSE) was combined in two ways: first, full ISIS localization plus a frequency-selective spin-echo and second, two-dimensional (2D) ISIS plus a frequency-selective excitation and slice-selective refocusing. The techniques were evaluated at 3 T in phantoms and human subjects in comparison to standard techniques with water presaturation or metabolite-cycling. ISIS included gradient-modulated offset-independent adiabatic (GOIA)-type adiabatic inversion pulses; echo times were 8-10 ms. RESULTS: The novel 2D and 3D I-CSE methods yield upfield spectra that are comparable to those from standard MRS, except for shorter echo times and a limited frequency range. On the downfield/high-frequency side, they yield much more signal for exchangeable protons when compared to MRS with water presaturation or metabolite-cycling and longer echo times. CONCLUSION: Novel non-water-excitation MRS sequences offer substantial benefits for the detection of metabolite signals that are otherwise suppressed by saturation transfer from water. Avoiding water saturation and using very short echo times allows direct observation of faster exchanging moieties than was previously possible at 3 T and additionally makes the methods less susceptible to fast T2 relaxation.

Emerging MRI Techniques to Redefine Treatment Response in Patients With Glioblastoma.

Glioblastoma is the most common and most malignant primary brain tumor. Despite aggressive multimodal treatment, its prognosis remains poor. Even with continuous developments in MRI, which has provided us with newer insights into the diagnosis and understanding of tumor biology, response assessment in the posttherapy setting remains challenging. We believe that the integration of additional information from advanced neuroimaging techniques can further improve the diagnostic accuracy of conventional MRI. In this article, we review the utility of advanced neuroimaging techniques such as diffusion-weighted imaging, diffusion tensor imaging, perfusion-weighted imaging, proton magnetic resonance spectroscopy, and chemical exchange saturation transfer in characterizing and evaluating treatment response in patients with glioblastoma. We will also discuss the existing challenges and limitations of using these techniques in clinical settings and possible solutions to avoiding pitfalls in study design, data acquisition, and analysis for future studies. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:978-997.

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.

Binswanger's disease: biomarkers in the inflammatory form of vascular cognitive impairment and dementia.

Vascular cognitive impairment and dementia (VCID) is a major public health concern because of the increased incidence of vascular disease in the aging population and the impact of vascular disease on Alzheimer's disease. VCID is a heterogeneous group of diseases for which there are no proven treatments. Biomarkers can be used to select more homogeneous populations. Small vessel disease is the most prevalent form of VCID and is the optimal form for treatment trials because there is a progressive course with characteristic pathological changes. Subcortical ischemic vascular disease of the Binswanger type (SIVD-BD) has a characteristic set of features that can be used both to identify patients and to follow treatment. SIVD-BD patients have clinical, neuropsychological, cerebrospinal fluid (CSF) and imaging features that can be used as biomarkers. No one feature is diagnostic, but a multimodal approach defines the SIVD-BD spectrum disorder. The most important features are large white matter lesions with axonal damage, blood-brain barrier disruption as shown by magnetic resonance imaging and CSF, and neuropsychological evidence of executive dysfunction. We have used these features to create a Binswanger Disease Scale and a probability of SIVD-BD, using a machine-learning algorithm. The patients discussed in this review are derived from published studies. Biomarkers not only aid in early diagnosis before the disease process has progressed too far for treatment, but also can indicate response to treatment. Refining the use of biomarkers will allow dementia treatment to enter the era of precision medicine. This article is part of the Special Issue "Vascular Dementia".

The role of MRI in understanding the underlying mechanisms in obesity associated diseases.

Obesity and its possible association with diseases including diabetes and cardiovascular diseases have been studied for decades for its impact on healthcare. Recent studies clearly indicate the need for developing accurate and reproducible methodologies for assessing body fat content and distribution. Body fat distribution plays a significant role in developing an insight in the underlying mechanisms in which adipose tissue is linked with various diseases. Among imaging technologies including computerized axial tomography (CAT or CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS), MRI and MRS seem to be the best emerging techniques and together are being considered as the gold standard for body fat content and distribution. This paper reviews studies up to the present time involving different methodologies of these two emerging technologies and presents the basic concepts of MRI and MRS with required novel image analysis techniques in accurate, quantitative, and direct assessment of body fat content and distribution. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

Elucidation of the downfield spectrum of human brain at 7 T using multiple inversion recovery delays and echo times.

PURPOSE: To characterize the downfield spectrum at 5-10 ppm in the human brain at a high magnetic field of 7 T. Knowledge of relaxation parameters is of interest for spectroscopy as well as chemical exchange-dependent saturation transfer experiments. METHODS: Water-suppressed spectra were recorded as echo time and inversion time series in healthy volunteers to investigate T2 and T1 values of downfield peaks in gray matter at 7T. The spectra were fitted in a two-dimensional fashion to a heuristic model of a series of Voigt lines, and the relaxation times were obtained for 12 peaks of interest. RESULTS: The mean T2 values averaged over the volunteers ranged from 24 to 158 ms, whereas the mean T1 values ranged from 0.22 to 2.40 s. Spectra of specific inversion and echo times revealed superposition of the amide peaks of N-acetylaspartate with short T2 and an inhomogeneously broadened component with longer T2 . CONCLUSIONS: T2 values were shorter than expected for most peaks, whereas T1 values had a very wide range; shorter relaxation times for some peaks suggests the presence of macromolecules. Most of the larger peaks seemed to be composed of overlapping components, because the Gaussian widths in the Voigt line shape descriptions were larger than expected based on field inhomogeneities. Magn Reson Med 78:11-19, 2016. © 2017 International Society for Magnetic Resonance in Medicine.

Qualitative 3-T Proton MR Spectroscopy for the Characterization of Musculoskeletal Neoplasms: Update on Diagnostic Performance and Indications.

OBJECTIVE: The objective of our study was to evaluate the diagnostic performance of qualitative 3-T proton MR spectroscopy (1H-MRS) for the characterization of musculoskeletal neoplasms. SUBJECTS AND METHODS: Proton MRS studies of 74 patients (76 lesions) with a histologically confirmed musculoskeletal neoplasm or neoplasms were prospectively included in this study. All studies were performed using a 3-T MRI scanner. Spectra were analyzed with conventional MRI software provided by the fabricant and with dedicated independent MRS software. Spectra were evaluated visually for the presence or absence of a choline peak at 3.2 ppm. The presence of a choline peak was considered indicative of malignancy. The influences of tumor origin and spectral quality on diagnostic performance were considered. RESULTS: Diagnostic performance was similar with both software used (κ = 0.97). Qualitative 1H-MRS failed to differentiate benign from malignant bone tumors regardless of the application of quality criteria (best sensitivity and specificity, 50.0% and 61.5%, respectively). Diagnostic performance was better with soft-tissue lesions, but the specificity remained low (best sensitivity and specificity, 82.4% and 64.3%, respectively). The application of spectral quality criteria for the evaluation of soft-tissue tumors led to the exclusion of 35.4% of the evaluated spectra. CONCLUSION: Qualitative 3-T 1H-MRS cannot be used to characterize bone tumors. This technique has good sensitivity but poor specificity for the characterization of soft-tissue lesions.

Changes of brain metabolite concentrations during maturation in different brain regions measured by chemical shift imaging.

INTRODUCTION: We examined the effect of maturation on the regional distribution of brain metabolite concentrations using multivoxel chemical shift imaging. METHODS: From our pool of pediatric MRI examinations, we retrospectively selected patients showing a normal cerebral MRI scan or no pathologic signal abnormalities at the level of the two-dimensional 1H MRS-CSI sequence and an age-appropriate global neurological development, except for focal neurological deficits. Seventy-one patients (4.5 months-20 years) were identified. Using LC Model, spectra were evaluated from voxels in the white matter, caudate head, and corpus callosum. RESULTS: The concentration of total N-acetylaspartate increased in all regions during infancy and childhood except in the right caudate head where it remained constant. The concentration of total creatine decreased in the caudate nucleus and splenium and minimally in the frontal white matter and genu. It remained largely constant in the parietal white matter. The concentration of choline-containing compounds had the tendency to decrease in all regions except in the parietal white matter where it remained constant. The concentration of myoinositol decreased slightly in the splenium and right frontal white matter, remained constant on the left side and in the caudate nucleus, and rose slightly in the parietal white matter and genu. CONCLUSION: CSI determined metabolite concentrations in multiple cerebral regions during routine MRI. The obtained data will be helpful in future pediatric CSI measurements deciding whether the ratios of the main metabolites are within the range of normal values or have to be considered as probably pathologic.

Influence of muscle fiber orientation on water and metabolite relaxation times, magnetization transfer, and visibility in human skeletal muscle.

PURPOSE: To gain a deeper understanding of the influence of skeletal muscle fiber orientation on metabolite visibility, magnetization transfer from water, and water proton relaxation rates in (1)H MR spectra. METHODS: Non-water-suppressed MR spectroscopy was performed in tibialis anterior muscle (TA) of 10 healthy adults, with the TA oriented either parallel or at the magic angle to the 3T field. Spectra were acquired with metabolite-cycled PRESS, and water inversion from 50 to 2510 ms before excitation. Water proton T2 relaxation was sampled with STEAM with echo times from 12 to 272 ms. RESULTS: Apparent concentrations of total creatine (tCr), taurine, and trimethylammonium compounds were reduced by 29% to 67% when TA was parallel to B0. Both tCr peak areas were strongly correlated to the methylene peak splitting. Magnetization transfer rates from water to tCr CH3 were not significantly different between orientations. Water T1s were similar between orientations, but T2s were statistically significantly shorter by 1 ms in the parallel orientation (P = 0.002). CONCLUSION: Muscle metabolite visibilities in MR spectroscopy and water T2 times depend substantially on muscle fiber orientation relative to B0 . In contrast, magnetization transfer rates appear to depend on muscle composition, rather than fiber orientation.

Proton MR Spectroscopy for Monitoring Pathologic Changes in the Substantia Nigra and Globus Pallidus in Parkinson Disease.

OBJECTIVE: This retrospective study aimed to examine the relationship between the ratio of N-acetyl aspartate (NAA) to creatine in the substantia nigra (SN) and globus pallidus (GP) and the Hoehn-Yahr stage and Unified Parkinson Disease Rating Scale (UPDRS) score determined for patients with Parkinson disease (PD). MATERIALS AND METHODS: Thirty patients with PD who underwent proton MR spectroscopy ((1)H-MRS) and for whom a Hoehn-Yahr stage and a UPDRS score for PD were determined were retrospectively reviewed. Hydrogen-1-MRS was used to measure the metabolite levels in the bilateral SN and GP. RESULTS: The mean (± SD) age of the patients was 67.7 (± 10.6) years. The mean UPDRS score was 40.5 ± 13.9. Fourteen patients had PD of Hoehn-Yahr stages 1-2, and 16 patients had PD of Hoehn-Yahr stages 3-5. The NC ratio (the NAA-to-creatine ratio for the initially symptomatic side or the body divided by the NAA-to-creatine ratio for the contralateral side) for the bilateral GP (BGPNC) was significantly lower in the patients with stages 1-2 PD than in the patients with stages 3-5 PD (0.68 ± 0.23 vs 0.84 ± 0.11; p = 0.023). The NAA-to-creatine ratio for the initially symptomatic side of the SN was negatively correlated with the UPDRS score (r = -0.379; p = 0.039). CONCLUSION: In early PD, the changes in the GP are more pronounced on the side affected at the onset of PD, which may contribute to the development of asymmetric symptoms and signs. Hydrogen-1-MRS shows promise as a modality for evaluating PD.

Short- and long-term reproducibility of marrow adipose tissue quantification by 1H-MR spectroscopy.

OBJECTIVE: To assess short- and long-term reproducibility of marrow adipose tissue (MAT) quantification by 1H-MR spectroscopy. MATERIALS AND METHODS: Our study was IRB-approved and HIPAA compliant. Written informed consent was obtained. We studied 20 overweight/obese but otherwise healthy subjects (12 female, 8 male) with a mean age of 37 ± 6 years. All subjects underwent proton magnetic resonance spectroscopy (1H-MRS) of the fourth lumbar vertebral body using a single-voxel point-resolved spatially localized spectroscopy sequence without water suppression at 3 T. Measurements were repeated after 6 weeks and 6 months using identical scanning protocols. The following clinical parameters were collected, weight, BMI, exercise status, and trabecular bone mineral density (BMD), by quantitative computed tomography. Short- (baseline, 6 weeks) and long-term (baseline, 6 months) reproducibility of MAT was assessed by the coefficient of variance (CV), standard deviation (SD), and interclass correlation coefficients (ICCs). Short- and long-term changes in clinical parameters were assessed by paired t-test. RESULTS: For short-term reproducibility between baseline and 6-week scans, the CV was 9.9 %, SD was 0.08, and ICC was 0.97 (95 % CI 0.94-099). For long-term reproducibility between baseline and 6-month scans, the CV was 12.0 %, SD was 0.10, and ICC was 0.95 (95 % CI 0.88 to 0.98). There was no significant short- or long-term change in clinical parameters (weight, BMI, exercise status, BMD) (p > 0.2). CONCLUSION: 1H-MRS is a reproducible method for short- and long-term quantification of MAT. Our results can guide sample size calculations for interventional and longitudinal studies.

In vivo proton MR spectroscopy of pancreatic neuroendocrine tumors in a multiple endocrine neoplasia type 1 conditional knockout mouse model.

PURPOSE: MR spectroscopy (MRS) can improve diagnosis and follow treatment in cancer. However, no study has yet reported application of in vivo (1)H-MRS in malignant pancreatic lesions. This study quantitatively determined whether in vivo (1)H-MRS on multiple endocrine neoplasia type 1 (Men1) conditional knockout (KO) mice and their wild type (WT) littermates could detect differences in total choline (tCho) levels between tumor and control pancreas. METHODS: Relative tCho levels in pancreatic tumors or pancreata from KO and WT mice were determined using in vivo (1)H-MRS at 9.4 T. The levels of Cho-containing compounds were also quantified using in vitro (1)H-NMR on extracts of pancreatic tissues from KO and WT mice, respectively, and on extracts of pancreatic tissues from patients with pancreatic neuroendocrine tumors (PNETs). RESULTS: tCho levels measured by in vivo (1)H-MRS were significantly higher in PNETs from KO mice compared to the normal pancreas from WT mice. The elevated choline-containing compounds were also identified in pancreatic tumors from KO mice and tissues from patients with PNETs via in vitro (1)H-NMR. CONCLUSION: These results indicate the potential use of tCho levels estimated via in vivo (1)H-MRS in differentiating malignant pancreatic tumors from benign tumors.

Whole-brain quantitative mapping of metabolites using short echo three-dimensional proton MRSI.

BACKGROUND: To improve the extent over which whole brain quantitative three-dimensional (3D) magnetic resonance spectroscopic imaging (MRSI) maps can be obtained and be used to explore brain metabolism in a population of healthy volunteers. METHODS: Two short echo time (20 ms) acquisitions of 3D echo planar spectroscopic imaging at two orientations, one in the anterior commissure-posterior commissure (AC-PC) plane and the second tilted in the AC-PC +15° plane were obtained at 3 Tesla in a group of 10 healthy volunteers. B1 (+) , B1 (-) , and B0 correction procedures and normalization of metabolite signals with quantitative water proton density measurements were performed. A combination of the two spatially normalized 3D-MRSI, using a weighted mean based on the pixel wise standard deviation metabolic maps of each orientation obtained from the whole group, provided metabolite maps for each subject allowing regional metabolic profiles of all parcels of the automated anatomical labeling (AAL) atlas to be obtained. RESULTS: The combined metabolite maps derived from the two acquisitions reduced the regional intersubject variance. The numbers of AAL regions showing N-acetyl aspartate (NAA) SD/Mean ratios lower than 30% increased from 17 in the AC-PC orientation and 41 in the AC-PC+15° orientation, to a value of 76 regions of 116 for the combined NAA maps. Quantitatively, regional differences in absolute metabolite concentrations (mM) over the whole brain were depicted such as in the GM of frontal lobes (cNAA = 10.03 + 1.71; cCho = 1.78 ± 0.55; cCr = 7.29 ± 1.69; cmIns = 5.30 ± 2.67) and in cerebellum (cNAA = 5.28 ± 1.77; cCho = 1.60 ± 0.41; cCr = 6.95 ± 2.15; cmIns = 3.60 ± 0.74). CONCLUSION: A double-angulation acquisition enables improved metabolic characterization over a wide volume of the brain.