Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Concentration of Gallbladder Phosphatidylcholine in Cholangiopathies: A Phosphorus-31 Magnetic Resonance Spectroscopy Pilot Study.

BACKGROUND: Biliary phosphatidylcholine (PtdC) concentration plays a role in the pathogenesis of bile duct diseases. In vivo phosphorus-31 magnetic resonance spectroscopy (31 P-MRS) at 7 T offers the possibility to assess this concentration noninvasively with high spectral resolution and signal intensity. PURPOSE: Comparison of PtdC levels of cholangiopathic patient groups to a control group using a measured T1 relaxation time of PtdC in healthy subjects. STUDY TYPE: Case control. SUBJECTS: Two patient groups with primary sclerosing cholangitis (PSC, 2f/3 m; age: 43 ± 7 years) and primary biliary cholangitis (PBC, 4f/2 m; age: 57 ± 6 years), and a healthy control group (CON, 2f/3 m; age: 38 ± 7 years). Ten healthy subjects for the assessment of the T1 relaxation time of PtdC. FIELD STRENGTH/SEQUENCE: A 3D phase-encoded pulse-acquire 31 P-MRSI sequence for PtdC quantification and a 1D image-selected in vivo 31 P spectroscopy for T1 estimation at 7 T, and a T2-weighted half-Fourier single-shot turbo spin echo MRI sequence for volumetry at 3 T. ASSESSMENT: Calculation of gallbladder volumes and PtdC concentration in groups using hepatic gamma-adenosine triphosphate signal as an internal reference and correction for insufficient relaxation of PtdC with a T1 value assessed in healthy subjects. STATISTICAL TESTS: Group comparison of PtdC content and gallbladder volumes of the PSC/PBC and CON group using Student's t-tests with a significance level of 5%. RESULTS: PtdC T1 value of 357 ± 85 msec in the gallbladder. Significant lower PtdC content for the PSC group, and for the female subgroup of the PBC group compared to the CON group (PSC/CON: 5.74 ± 0.73 mM vs. 9.64 ± 0.97 mM, PBC(f)/CON: 5.77 ± 1.44 mM vs. 9.64 ± 0.97 mM). Significant higher gallbladder volumes of the patient groups compared to the CON group (PSC/CON: 66.3 ± 15.8 mL vs. 20.9 ± 2.2 mL, PBC/CON: 49.8 ± 18.2 mL vs. 20.9 ± 2.2 mL). DATA CONCLUSION: This study demonstrated the application of a 31 P-MRSI protocol for the quantification of PtdC in the human gallbladder at 7 T. Observed differences in PtdC concentration suggest that this metabolite could serve as a biomarker for specific hepatobiliary disorders. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

A systematic review on the use of quantitative imaging to detect cancer therapy adverse effects in normal-appearing brain tissue.

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research.

Ankylosing spondylitis on unidentified individual from early modern times found in reformed church (Silická Brezová, Slovakia): a case-based review.

The grave situated in the central part of the reformed church in Silická Brezová in Slovakia contained the human skeletal remains of one individual. The aim of this study was to confirm the presence of ankylosing spondylitis on these skeletal remains. Determine the sex, age at death, stature, and ancestry of the individual by anthropological methods, and also record and identify other pathological manifestations of diseases. A macroscopic examination has been carried out, with the analysis of the palaeopathological conditions of the remains, and subsequently an X-ray and CT completed analysis. The skeleton belonged to a male of European origin, aged between 45 and 60 years at the time of death. Stature calculated from the maximal length of his femur was 163.12 ± 3.48 cm. Pathological features were identified on the many bones. Ankylosis affected almost the whole spinal cord, including the sacroiliac joints. The skeleton also presented the manifestation of many entheseal changes. Presence of the ankylosing spondylitis was confirmed by a combination of standard anthropological methods and modern diagnostic methods (X-ray and CT analysis). It is a specific disease with a prevalence between 0.1 and 1% worldwide. There is a potential for further genetic research to determine the degree of genetic relatedness with an individual living in this village who has been diagnosed with the same disease.

In Vivo 1 H MR Spectroscopy of Biliary Components of Human Gallbladder at 7T.

BACKGROUND: Previous in vivo proton MR spectroscopy (MRS) studies have demonstrated the possibility of quantifying amide groups of conjugated bile acids (NHCBA), olefinic lipids and cholesterol (OLC), choline-containing phospholipids (CCPLs), taurine and glycine conjugated bile acids (TCBA, GCBA), methylene group of lipids (ML), and methyl groups of bile acids, lipids, and cholesterol (BALC1.0, BALC0.9, and TBAC) in the gallbladder, which may be useful for the study of cholestatic diseases and cholangiopathies. However, these studies were performed at 1.5T and 3T, and higher magnetic fields may offer improved spectral resolution and signal intensity. PURPOSE: To develop a method for gallbladder MRS at 7T. STUDY TYPE: Retrospective, technical development. POPULATION: Ten healthy subjects (five males and five females), two patients with primary biliary cholangitis (PBC) (one male and one female), and one patient with primary sclerosing cholangitis (PSC) (female). FIELD STRENGTH/SEQUENCE: Free-breathing single-voxel MRS with a modified stimulated echo acquisition mode (STEAM) sequence at 7T. ASSESSMENT: Postprocessing was based on the T2 relaxation of water in the gallbladder and in the liver. Concentrations of biliary components were calculated using water signal. All data were corrected for T2 relaxation times measured in healthy subjects. STATISTICAL TESTS: The range of T2 relaxation time and concentration per bile component, and the resulting mean and standard deviation, were calculated. RESULTS: The concentrations of gallbladder components in healthy subjects were: NHCBA: 93 ± 66 mM, OLC: 154 ± 124 mM, CCPL: 42 ± 17 mM, TCBA: 48 ± 35 mM, GCBA: 67 ± 32 mM, ML: 740 ± 391 mM, BALC1.0: 175 ± 92 mM, BALC0.9: 260 ± 138 mM, and TBAC: 153 ± 90 mM. Mean concentrations of all bile components were found to be lower in patients. DATA CONCLUSION: This work provides a protocol for designing future MRS investigations of the bile system in vivo. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY STAGE: 1.

Absolute Quantification of Phosphor-Containing Metabolites in the Liver Using 31 P MRSI and Hepatic Lipid Volume Correction at 7T Suggests No Dependence on Body Mass Index or Age.

BACKGROUND: Hepatic disorders are often associated with changes in the concentration of phosphorus-31 (31 P) metabolites. Absolute quantification offers a way to assess those metabolites directly but introduces obstacles, especially at higher field strengths (B0 ≥ 7T). PURPOSE: To introduce a feasible method for in vivo absolute quantification of hepatic 31 P metabolites and assess its clinical value by probing differences related to volunteers' age and body mass index (BMI). STUDY TYPE: Prospective cohort. SUBJECTS/PHANTOMS: Four healthy volunteers included in the reproducibility study and 19 healthy subjects arranged into three subgroups according to BMI and age. Phantoms containing 31 P solution for correction and validation. FIELD STRENGTH/SEQUENCE: Phase-encoded 3D pulse-acquire chemical shift imaging for 31 P and single-volume 1 H spectroscopy to assess the hepatocellular lipid content at 7T. ASSESSMENT: A phantom replacement method was used. Spectra located in the liver with sufficient signal-to-noise ratio and no contamination from muscle tissue, were used to calculate following metabolite concentrations: adenosine triphosphates (γ- and α-ATP); glycerophosphocholine (GPC); glycerophosphoethanolamine (GPE); inorganic phosphate (Pi ); phosphocholine (PC); phosphoethanolamine (PE); uridine diphosphate-glucose (UDPG); nicotinamide adenine dinucleotide-phosphate (NADH); and phosphatidylcholine (PtdC). Correction for hepatic lipid volume fraction (HLVF) was performed. STATISTICAL TESTS: Differences assessed by analysis of variance with Bonferroni correction for multiple comparison and with a Student's t-test when appropriate. RESULTS: The concentrations for the young lean group corrected for HLVF were 2.56 ± 0.10 mM for γ-ATP (mean ± standard deviation), α-ATP: 2.42 ± 0.15 mM, GPC: 3.31 ± 0.27 mM, GPE: 3.38 ± 0.87 mM, Pi : 1.42 ± 0.20 mM, PC: 1.47 ± 0.24 mM, PE: 1.61 ± 0.20 mM, UDPG: 0.74 ± 0.17 mM, NADH: 1.21 ± 0.38 mM, and PtdC: 0.43 ± 0.10 mM. Differences found in ATP levels between lean and overweight volunteers vanished after HLVF correction. DATA CONCLUSION: Exploiting the excellent spectral resolution at 7T and using the phantom replacement method, we were able to quantify up to 10 31 P-containing hepatic metabolites. The combination of 31 P magnetic resonance spectroscopy imaging data acquisition and HLVF correction was not able to show a possible dependence of 31 P metabolite concentrations on BMI or age, in the small healthy population used in this study. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:597-607.

Effect of Rehabilitation on Fatigue Level in Patients with Multiple Sclerosis.

BACKGROUND The objective of this study was to evaluate the effect of a rehabilitation program in changing the perception of fatigue in patients with multiple sclerosis. MATERIAL AND METHODS The study involved 65 respondents/patients with clinically confirmed multiple sclerosis (54 women, 11 men, average age 46.49 years). The evaluation of the effects of fatigue on the physical, psychological, and psychosocial aspects of life was assessed using the Modified Fatigue Impact Scale (MFIS). To test the effectiveness of the neurorehabilitation program, we enrolled 2 groups: the experimental group (EG, n=32, 29 women, 3 men, Expanded Disability Status Scale (EDSS) 4.8 average, SD±1.77, min. 1.5 max 8.0) participated in the intervention and rehabilitation program over a period of 12 weeks and the control group (CG, n=33, 25 women, 8 men. EDSS average 5.12±1.74 SD, min. 2.0 max. 8.0). Each group of patients was divided into 3 sub-groups according to the severity of EDSS: a) 1-3.5, b) 4-6, and c) 6.5-8. For the statistical evaluation of the significance of the observed changes, the MANOVA/ANOVA model was used. RESULTS Between the input and output assessment of the MFIS individual areas questionnaire between the EG and the CG, there existed a statistically significant in the physical area (p<0.000), psychological area (p<0.000), and psychosocial area (p=0.002). CONCLUSIONS Our results support the importance of an active approach in patients with multiple sclerosis using individualized rehabilitation intervention programs.

Gliptin therapy reduces hepatic and myocardial fat in type 2 diabetic patients.

BACKGROUND: Increased hepatic fat and cardiac fat are common in patients with type 2 diabetes mellitus (T2DM) and are associated with a greater risk of liver fibrosis and cardiovascular (CV) events. Sex-specific differences of dipeptidyl peptidase-four (DPP-4) inhibitor effects on hepatic (HCL) and myocardial fat content (MYCL) have not yet been evaluated. METHOD: Forty-one T2DM patients (20 male, 21 female) received a gliptin add-on therapy if HbA1c goals were not reached under metformin monotherapy. They underwent cardiac and liver magnetic resonance tomography and spectroscopy before and 6 months after therapy initiation. Plasma samples were analysed for the growth differentiation factor 15 (GDF-15), a novel marker for cardiovascular risk. RESULTS: Thirty-eight patients on gliptin therapy completed the study. We observed a positive correlation between MYCL and HCL before therapy (R = 0·41, P = 0·05). After 6 months of therapy, we noticed a significant weight reduction in women only (P = 0·02) whereas waist circumference decreased similarly in both sexes. HbA1c sunk significantly in both sexes (P = 0·002). HCL decreased significantly (P = 0·0004), with women featuring higher basal HCL (P < 0·05). MYCL decreased in women only (P = 0·01) and GDF-15 comparably in both sexes (P < 0·05). CONCLUSIONS: 6 months of DPP-4-therapy led to a significant overall decrease in HCL and body weight such as a reduction of MYCL only in women. This preliminary data set could implicate that gliptin may be a feasible therapy option in fatty liver patients with diabetes potentially including positive effects on cardiovascular function particularly in women.

In-vivo31P-MRS of skeletal muscle and liver: A way for non-invasive assessment of their metabolism.

In addition to direct assessment of high energy phosphorus containing metabolite content within tissues, phosphorus magnetic resonance spectroscopy (31P-MRS) provides options to measure phospholipid metabolites and cellular pH, as well as the kinetics of chemical reactions of energy metabolism in vivo. Even though the great potential of 31P-MR was recognized over 30 years ago, modern MR systems, as well as new, dedicated hardware and measurement techniques provide further opportunities for research of human biochemistry. This paper presents a methodological overview of the 31P-MR techniques that can be used for basic, physiological, or clinical research of human skeletal muscle and liver in vivo. Practical issues of 31P-MRS experiments and examples of potential applications are also provided. As signal localization is essential for liver 31P-MRS and is important for dynamic muscle examinations as well, typical localization strategies for 31P-MR are also described.

Feasibility and repeatability of localized (31) P-MRS four-angle saturation transfer (FAST) of the human gastrocnemius muscle using a surface coil at 7 T.

Phosphorus ((31) P) MRS, combined with saturation transfer (ST), provides non-invasive insight into muscle energy metabolism. However, even at 7 T, the standard ST method with T1 (app) measured by inversion recovery takes about 10 min, making it impractical for dynamic examinations. An alternative method, i.e. four-angle saturation transfer (FAST), can shorten the examination time. The aim of this study was to test the feasibility, repeatability, and possible time resolution of the localized FAST technique measurement on an ultra-high-field MR system, to accelerate the measurement of both Pi -to-ATP and PCr-to-ATP reaction rates in the human gastrocnemius muscle and to test the feasibility of using the FAST method for dynamic measurements. We measured the exchange rates and metabolic fluxes in the gastrocnemius muscle of eight healthy subjects at 7 T with the depth-resolved surface coil MRS (DRESS)-localized FAST method. For comparison, a standard ST localized method was also used. The measurement time for the localized FAST experiment was 3.5 min compared with the 10 min for the standard localized ST experiment. In addition, in five healthy volunteers, Pi -to-ATP and PCr-to-ATP metabolic fluxes were measured in the gastrocnemius muscle at rest and during plantar flexion by the DRESS-localized FAST method. The repeatability of PCr-to-ATP and Pi -to-ATP exchange rate constants, determined by the slab-selective localized FAST method at 7 T, is high, as the coefficients of variation remained below 20%, and the results of the exchange rates measured with the FAST method are comparable to those measured with standard ST. During physical activity, the PCr-to-ATP metabolic flux decreased (from FCK = 8.21 ± 1.15 mM s(-1) to FCK = 3.86 ± 1.38 mM s(-1) ) and the Pi -to-ATP flux increased (from FATP = 0.43 ± 0.14 mM s(-1) to FATP = 0.74 ± 0.13 mM s(-1) ). In conclusion, we could demonstrate that measurements in the gastrocnemius muscle are feasible at rest and are short enough to be used during exercise with the DRESS-localized FAST method at 7 T.

Improved spectral resolution and high reliability of in vivo (1) H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle.

The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by (1) H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T1 measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times - before and twice after (approximately 20 and 40 min) a 1-h submaximal street run and additional toe-hopping. The measured T1 relaxation times for the C2-H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T2 times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by (1) H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise-induced change in pH. Our results support the application of the MRS-based assessment of carnosine for pH measurement in muscle compartments.

Dynamic 31 P-MRSI using spiral spectroscopic imaging can map mitochondrial capacity in muscles of the human calf during plantar flexion exercise at 7 T.

Phosphorus MRSI (31 P-MRSI) using a spiral-trajectory readout at 7 T was developed for high temporal resolution mapping of the mitochondrial capacity of exercising human skeletal muscle. The sensitivity and localization accuracy of the method was investigated in phantoms. In vivo performance was assessed in 12 volunteers, who performed a plantar flexion exercise inside a whole-body 7 T MR scanner using an MR-compatible ergometer and a surface coil. In five volunteers the knee was flexed (~60°) to shift the major workload from the gastrocnemii to the soleus muscle. Spiral-encoded MRSI provided 16-25 times faster mapping with a better point spread function than elliptical phase-encoded MRSI with the same matrix size. The inevitable trade-off for the increased temporal resolution was a reduced signal-to-noise ratio, but this was acceptable. The phosphocreatine (PCr) depletion caused by exercise at 0° knee angulation was significantly higher in both gastrocnemii than in the soleus (i.e. 64.8 ± 19.6% and 65.9 ± 23.6% in gastrocnemius lateralis and medialis versus 15.3 ± 8.4% in the soleus). Spiral-encoded 31 P-MRSI is a powerful tool for dynamic mapping of exercising muscle oxidative metabolism, including localized assessment of PCr concentrations, pH and maximal oxidative flux with high temporal and spatial resolution.

Mapping of brain macromolecules and their use for spectral processing of (1)H-MRSI data with an ultra-short acquisition delay at 7 T.

Long echo time (TE) MR spectroscopy (MRS) sequences are sensitive only to metabolites of low molecular weight. At shorter TE, significantly more metabolite signals are detectable, including broad signals of high-molecular-weight macromolecules (MMs). Although the presence of MM resonances can bias metabolite quantification at short TE, proper quantification of MMs is important since MMs themselves may serve as potentially valuable biomarkers for many pathologies. We have therefore developed an FID-based 2D-MR Spectroscopic Imaging (2D-MRSI) sequence to map MMs in healthy brain tissue at 7 T within a scan time of ~17 min and a repetition time of 879 ms. This 2D-MRSI technique provides MM maps over a whole slice (i.e., including cortical gray matter) at an ultra-short acquisition delay of 1.3 ms, using double inversion for efficient nulling of low-molecular-weight metabolites. The optimal sequence parameters were estimated using Bloch simulations, phantom testing, and in vivo validation. The acquired in vivo MM spectra (n=6) included nine distinct MM peaks in the range of ~0.9-3.7 ppm. The measured average MM spectrum was incorporated into the LCModel basis set and utilized for further quantification of MRSI data sets without metabolite nulling, which were acquired in five additional volunteers. The quantification results for two basis sets, one including the MMs and one without MM spectrum, were compared. Due to the high spectral resolution and full signal detection provided by the FID-MRSI sequence, we could successfully map five important brain metabolites. Most quantified metabolite signal amplitudes were significantly lower since the inclusion of MMs into the basis set corrected the overestimation of metabolite signals. The precision of fit (i.e., Cramér Rao lower bounds) remained unchanged. Our MM maps show that the overall MM contribution was higher in gray matter than in white matter. In conclusion, the acquired MM spectrum improved the accuracy of metabolite quantification and allowed the acquisition of high spatial resolution maps of five major brain metabolites and also MMs.

Lipid suppression via double inversion recovery with symmetric frequency sweep for robust 2D-GRAPPA-accelerated MRSI of the brain at 7 T.

This work presents a new approach for high-resolution MRSI of the brain at 7 T in clinically feasible measurement times. Two major problems of MRSI are the long scan times for large matrix sizes and the possible spectral contamination by the transcranial lipid signal. We propose a combination of free induction decay (FID)-MRSI with a short acquisition delay and acceleration via in-plane two-dimensional generalised autocalibrating partially parallel acquisition (2D-GRAPPA) with adiabatic double inversion recovery (IR)-based lipid suppression to allow robust high-resolution MRSI. We performed Bloch simulations to evaluate the magnetisation pathways of lipids and metabolites, and compared the results with phantom measurements. Acceleration factors in the range 2-25 were tested in a phantom. Five volunteers were scanned to verify the value of our MRSI method in vivo. GRAPPA artefacts that cause fold-in of transcranial lipids were suppressed via double IR, with a non-selective symmetric frequency sweep. The use of long, low-power inversion pulses (100 ms) reduced specific absorption rate requirements. The symmetric frequency sweep over both pulses provided good lipid suppression (>90%), in addition to a reduced loss in metabolite signal-to-noise ratio (SNR), compared with conventional IR suppression (52-70%). The metabolic mapping over the whole brain slice was not limited to a rectangular region of interest. 2D-GRAPPA provided acceleration up to a factor of nine for in vivo FID-MRSI without a substantial increase in g-factors (<1.1). A 64 × 64 matrix can be acquired with a common repetition time of ~1.3 s in only 8 min without lipid artefacts caused by acceleration. Overall, we present a fast and robust MRSI method, using combined double IR fat suppression and 2D-GRAPPA acceleration, which may be used in (pre)clinical studies of the brain at 7 T.

Ultrashort-TE stimulated echo acquisition mode (STEAM) improves the quantification of lipids and fatty acid chain unsaturation in the human liver at 7 T.

Ultrahigh-field, whole-body MR systems increase the signal-to-noise ratio (SNR) and improve the spectral resolution. Sequences with a short TE allow fast signal acquisition with low signal loss as a result of spin-spin relaxation. This is of particular importance in the liver for the precise quantification of the hepatocellular content of lipids (HCL). In this study, we introduce a spoiler Gradient-switching Ultrashort STimulated Echo AcqUisition (GUSTEAU) sequence, which is a modified version of a stimulated echo acquisition mode (STEAM) sequence, with a minimum TE of 6 ms. With the high spectral resolution at 7 T, the efficient elimination of water sidebands and the post-processing suppression of the water signal, we estimated the composition of fatty acids (FAs) via the detection of the olefinic lipid resonance and calculated the unsaturation index (UI) of hepatic FAs. The performance of the GUSTEAU sequence for the assessment of UI was validated against oil samples and provided excellent results in agreement with the data reported in the literature. When measuring HCL with GUSTEAU in 10 healthy volunteers, there was a high correlation between the results obtained at 7 and 3 T (R(2) = 0.961). The test-retest measurements yielded low coefficients of variation for HCL (4 ± 3%) and UI (11 ± 8%) when measured with the GUSTEAU sequence at 7 T. A negative correlation was found between UI and HCL (n = 10; p < 0.033). The ultrashort TE MRS sequence (GUSTEAU; TE = 6 ms) provided high repeatability for the assessment of HCL. The improved spectral resolution at 7 T with the elimination of water sidebands and the offline water subtraction also enabled an assessment of the unsaturation of FAs. This all highlights the potential use of this MRS acquisition scheme for studies of hepatic lipid composition in vivo.

Phosphatidylcholine contributes to in vivo (31)P MRS signal from the human liver.

OBJECTIVES: To demonstrate the overlap of the hepatic and bile phosphorus ((31)P) magnetic resonance (MR) spectra and provide evidence of phosphatidylcholine (PtdC) contribution to the in vivo hepatic (31)P MRS phosphodiester (PDE) signal, suggested in previous reports to be phosphoenolpyruvate (PEP). METHODS: Phantom measurements to assess the chemical shifts of PEP and PtdC signals were performed at 7 T. A retrospective analysis of hepatic 3D (31)P MR spectroscopic imaging (MRSI) data from 18 and five volunteers at 3 T and 7 T, respectively, was performed. Axial images were inspected for the presence of gallbladder, and PDE signals in representative spectra were quantified. RESULTS: Phantom experiments demonstrated the strong pH-dependence of the PEP chemical shift and proved the overlap of PtdC and PEP (~2 ppm relative to phosphocreatine) at hepatic pH. Gallbladder was covered in seven of 23 in vivo 3D-MRSI datasets. The PDE(gall)/γ-ATP(liver) ratio was 4.8-fold higher (p = 0.001) in the gallbladder (PDE(gall)/γ-ATP(liver) = 3.61 ± 0.79) than in the liver (PDE(liver)/γ-ATP(liver) = 0.75 ± 0.15). In vivo 7 T (31)P MRSI allowed good separation of PDE components. The gallbladder is a strong source of contamination in adjacent (31)P MR hepatic spectra due to biliary phosphatidylcholine. CONCLUSIONS: In vivo (31)P MR hepatic signal at 2.06 ppm may represent both phosphatidylcholine and phosphoenolpyruvate, with a higher phosphatidylcholine contribution due to its higher concentration. KEY POINTS: • In vivo (31)P MRS from the gallbladder shows a dominant biliary phosphatidylcholine signal at 2.06 ppm. • Intrahepatic (31)P MRS signal at 2.06 ppm may represent both intrahepatic phosphatidylcholine and phosphoenolpyruvate. • In vivo (31)P MRS has the potential to monitor hepatic phosphatidylcholine.

Dixon imaging-based partial volume correction improves quantification of choline detected by breast 3D-MRSI.

OBJECTIVES: Our aim was to develop a partial volume (PV) correction method of choline (Cho) signals detected by breast 3D-magnetic resonance spectroscopic imaging (3D-MRSI), using information from water/fat-Dixon MRI. METHODS: Following institutional review board approval, five breast cancer patients were measured at 3 T. 3D-MRSI (1 cm(3) resolution, duration ~11 min) and Dixon MRI (1 mm(3), ~2 min) were measured in vivo and in phantoms. Glandular/lesion tissue was segmented from water/fat-Dixon MRI and transformed to match the resolution of 3D-MRSI. The resulting PV values were used to correct Cho signals. Our method was validated on a two-compartment phantom (choline/water and oil). PV values were correlated with the spectroscopic water signal. Cho signal variability, caused by partial-water/fat content, was tested in 3D-MRSI voxels located in/near malignant lesions. RESULTS: Phantom measurements showed good correlation (r = 0.99) with quantified 3D-MRSI water signals, and better homogeneity after correction. The dependence of the quantified Cho signal on the water/fat voxel composition was significantly (p < 0.05) reduced using Dixon MRI-based PV correction, compared to the original uncorrected data (1.60-fold to 3.12-fold) in patients. CONCLUSIONS: The proposed method allows quantification of the Cho signal in glandular/lesion tissue independent of water/fat composition in breast 3D-MRSI. This can improve the reproducibility of breast 3D-MRSI, particularly important for therapy monitoring.

One-dimensional image-selected in vivo spectroscopy localized phosphorus saturation transfer at 7T.

PURPOSE: To evaluate the feasibility of a one-dimensional image-selected in vivo spectroscopy (1D-ISIS) saturation transfer (ST) sequence at 7T for localized in vivo measurements of energy metabolism in different tissues in clinically reasonable examination times. METHODS: The performance of a gradient offset independent adiabacity-based 1D-ISIS localization was tested on phantom and the localized ST sequence was compared with the nonlocalized version in vivo. We performed localized measurements of basal metabolism of human liver and different muscle groups of the calf. Localized ST experiments took 15-25 minutes. RESULTS: The selectivity of the 1D-ISIS sequence was 81.63% and the outer volume suppression was 97.57%. The ST parameters acquired with the 1D-ISIS sequence and with the nonlocalized acquisition in the muscle were not statistically different. The forward rate constants for phosphocreatine (PCr)-adenosine triphosphate (ATP) and inorganic phosphate (Pi)-ATP exchange reactions were measured in the soleus (kCK = 0.30 ± 0.06 s(-1) and kATP = 0.11 ± 0.02 s(-1) , respectively) and in the medial gastrocnemius (kCK = 0.27 ± 0.06 s(-1) and kATP = 0.09 ± 0.03s(-1) , respectively) in 15 minutes per muscle group. The corresponding fluxes were FCK = 6.26 ± 1.28 µmol/g/s, FATP = 0.22 ± 0.05 µmol/g/s and FCK = 6.29 ± 1.66 µmol/g/s, FATP = 0.21 ± 0.07 µmol/g/s, for soleus and gastrocnemius, respectively. The hepatic ATP synthesis measurement was feasible in 24 minutes. CONCLUSION: The fast assessment of PCr-ATP and Pi-ATP exchange rates at 7T makes the 1D-ISIS ST sequence a promising tool for examining local resting-state metabolism in clinically acceptable measurement times.

In vivo (31)P magnetic resonance spectroscopy of the human liver at 7 T: an initial experience.

Phosphorus ((31) P) MRS is a powerful tool for the non-invasive investigation of human liver metabolism. Four in vivo (31) P localization approaches (single voxel image selected in vivo spectroscopy (3D-ISIS), slab selective 1D-ISIS, 2D chemical shift imaging (CSI), and 3D-CSI) with different voxel volumes and acquisition times were demonstrated in nine healthy volunteers. Localization techniques provided comparable signal-to-noise ratios normalized for voxel volume and acquisition time differences, Cramer-Rao lower bounds (8.7 ± 3.3%1D-ISIS , 7.6 ± 2.5%3D-ISIS , 8.6 ± 4.2%2D-CSI , 10.3 ± 2.7%3D-CSI ), and linewidths (50 ± 24 Hz1D-ISIS , 34 ± 10 Hz3D-ISIS , 33 ± 10 Hz2D-CSI , 34 ± 11 Hz3D-CSI ). Longitudinal (T1 ) relaxation times of human liver metabolites at 7 T were assessed by 1D-ISIS inversion recovery in the same volunteers (n = 9). T1 relaxation times of hepatic (31) P metabolites at 7 T were the following: phosphorylethanolamine - 4.41 ± 1.55 s; phosphorylcholine - 3.74 ± 1.31 s; inorganic phosphate - 0.70 ± 0.33 s; glycerol 3-phosphorylethanolamine - 6.19 ± 0.91 s; glycerol 3-phosphorylcholine - 5.94 ± 0.73 s; γ-adenosine triphosphate (ATP) - 0.50 ± 0.08 s; α-ATP - 0.46 ± 0.07 s; ß-ATP - 0.56 ± 0.07 s. The improved spectral resolution at 7 T enabled separation of resonances in the phosphomonoester and phosphodiester spectral region as well as nicotinamide adenine dinucleotide and uridine diphosphoglucose signals. An additional resonance at 2.06 ppm previously assigned to phosphoenolpyruvate or phosphatidylcholine is also detectable. These are the first (31) P metabolite relaxation time measurements at 7 T in human liver, and they will help in the exploration of new, exciting questions in metabolic research with 7 T MR.