31-phosphorus Spectroscopy Research Articles

Role of Cardiac Energetics in Aortic Stenosis Disease Progression: Identifying the High-risk Metabolic Phenotype.

Severe aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and cardiac metabolic alterations with evidence of steatosis and impaired myocardial energetics. Despite this common phenotype, there is an unexplained and wide individual heterogeneity in the degree of hypertrophy and progression to myocardial fibrosis and heart failure. We sought to determine whether the cardiac metabolic state may underpin this variability. We recruited 74 asymptomatic participants with AS and 13 healthy volunteers. Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to adenosine triphosphate ratio. Myocardial lipid content was determined using proton spectroscopy. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging. Phosphocreatine/adenosine triphosphate was reduced early and significantly across the LV wall thickness quartiles (Q2, 1.50 [1.21-1.71] versus Q1, 1.64 [1.53-1.94]) with a progressive decline with increasing disease severity (Q4, 1.48 [1.18-1.70]; P=0.02). Myocardial triglyceride content levels were overall higher in all the quartiles with a significant increase seen across the AV pressure gradient quartiles (Q2, 1.36 [0.86-1.98] versus Q1, 1.03 [0.81-1.56]; P=0.034). While all AS groups had evidence of subclinical LV dysfunction with impaired strain parameters, impaired systolic longitudinal strain was related to the degree of energetic impairment (r=0.219; P=0.03). Phosphocreatine/adenosine triphosphate was not only an independent predictor of LV wall thickness (r=-0.20; P=0.04) but also strongly associated with myocardial fibrosis (r=-0.24; P=0.03), suggesting that metabolic changes play a role in disease progression. The metabolic and functional parameters showed comparable results when graded by clinical severity of AS. A gradient of myocardial energetic deficit and steatosis exists across the spectrum of hypertrophied AS hearts, and these metabolic changes precede irreversible LV remodeling and subclinical dysfunction. As such, cardiac metabolism may play an important and potentially causal role in disease progression.

Effect of chain transfer agents in polycarboxylate superplasticizer on slump‐retention of concrete

AbstractTwo types of slump‐retention polycarboxylate superplasticizers (PC‐M and PC‐S) were synthesized by using 3‐mercaptopropionic acid or sodium hypophosphite as chain transfer agents, the effects of polycarboxylate superplasticizers on slump‐retention of cement and concrete were investigated, and the mechanism of action and the structure of polycarboxylate superplasticizers were investigated by using conductivity, complexing Ca2+ concentration, gel permeation chromatography (GPC), nuclear magnetic resonance hydrogen spectroscopy (1H‐NMR), and nuclear magnetic resonance phosphorus spectroscopy (31P‐NMR). The results indicated that the slump flow of cement paste mixed with PC‐M was increased quickly within 60 min and then lost gradually, while PC‐S increased slowly and evenly within 240 min. The slump flow of concrete mixed with PC‐S reached 405 mm after 150 min, but the concrete mixed with PC‐M was almost no fluidity after 150 min. The conductivity of the PC‐M aqueous solution decreased quickly within 45 min, then slowly decreased, while the conductivity of the PC‐S aqueous solution decreased slowly within 180 min. PC‐M had a much greater complexation ability of Ca2+ than PC‐S. The composition and structure of the two slump‐retention polycarboxylate superplasticizers were altered by different chain transfer agents, and the hydrolysis‐adsorption capacity of each component was different. The rate of hydrolyzation‐adsorption of each component was PC‐M3 ≈ PC‐S3>PC‐M1>PC‐M2 ≈ PC‐S1>PC‐S2. The faster the adsorption rate, the faster the slump flow loss of concrete.

Phenotyping heart failure by cardiac magnetic resonance imaging of cardiac macro- and microscopic structure: state of the art review.

Heart failure demographics have evolved in past decades with the development of improved diagnostics, therapies, and prevention. Cardiac magnetic resonance (CMR) has developed in a similar timeframe to become the gold-standard non-invasive imaging modality for characterizing diseases causing heart failure. CMR techniques to assess cardiac morphology and function have progressed since their first use in the 1980s. Increasingly efficient acquisition protocols generate high spatial and temporal resolution images in less time. This has enabled new methods of characterizing cardiac systolic and diastolic function such as strain analysis, exercise real-time cine imaging and four-dimensional flow. A key strength of CMR is its ability to non-invasively interrogate the myocardial tissue composition. Gadolinium contrast agents revolutionized non-invasive cardiac imaging with the late gadolinium enhancement technique. Further advances enabled quantitative parametric mapping to increase sensitivity at detecting diffuse pathology. Novel methods such as diffusion tensor imaging and artificial intelligence-enhanced image generation are on the horizon. Magnetic resonance spectroscopy (MRS) provides a window into the molecular environment of the myocardium. Phosphorus (31P) spectroscopy can inform the status of cardiac energetics in health and disease. Proton (1H) spectroscopy complements this by measuring creatine and intramyocardial lipids. Hyperpolarized carbon (13C) spectroscopy is a novel method that could further our understanding of dynamic cardiac metabolism. CMR of other organs such as the lungs may add further depth into phenotypes of heart failure. The vast capabilities of CMR should be deployed and interpreted in context of current heart failure challenges.

Characterization and Geological Implications of Precambrian Calcite‐Hosted Phosphate

AbstractConstraints on marine phosphate availability and cycling directly inform our understanding of long‐term biological evolution. However, early Earth phosphate records are sparse, biased toward siliciclastic samples, and susceptible to post‐depositional modification. Well‐preserved shallow marine inorganic carbonate precipitates provide a complementary yet understudied record of phosphate cycling. We combined micro‐X‐ray fluorescence mapping, X‐ray absorption, and Nuclear Magnetic Resonance spectroscopy on samples of Precambrian syndepositional herringbone calcite (HBC) and microspar to characterize phosphorus speciation and distribution in these carbonate fabrics. Phosphorus spectroscopy from synthetic calcite, HBC, and microspar, is qualitatively consistent with a disordered distribution of phosphate. These characteristics are diagnostic of calcite‐hosted phosphate, which is pervasive at low concentrations in HBC and microspar. This study provides evidence that ancient, well‐preserved carbonate fabrics retain phosphate sourced from seawater and highlights the potential for an unaltered archive of marine phosphate concentration over geologic time.

Phosphorus metabolism in the brain of cognitively normal midlife individuals at risk for Alzheimer's disease

BackgroundNeurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphorus magnetic resonance spectroscopy (31P-MRS) and positron emission tomography (PET). MethodsWe measured 31P-MRS, fluorodeoxyglucose (FDG)-PET, and Pittsburgh Compound B (PiB)-PET in a cohort of 20 cognitively normal middle-aged adults at risk for AD. We assessed 31P-MRS reliability by scanning a separate cohort of 13 healthy volunteers twice each. We calculated the coefficient-of-variation (CV) of metabolite ratios phosphocreatine-to-adenosine triphosphate (PCr/α-ATP), inorganic phosphate (Pi)-to-α-ATP, and phosphomonoesters-to-phosphodiesters (PME/PDE), and pH in pre-defined brain regions. We performed linear regression analysis to determine the relationship between 31P measurements and tracer uptake, and Dunn's multiple comparison tests to investigate regional differences in phosphorus metabolism. Finally, we performed linear regression analysis on 31P-MRS measurements in both cohorts to investigate the relationship of phosphorus metabolism with age. ResultsMost regional 31P metabolite ratio and pH inter- and intra-day CVs were well below 10%. There was an inverse relationship between FDG-SUV levels and metabolite ratios PCr/α-ATP, Pi/α-ATP, and PME/PDE in several brain regions in the AD risk group. There were also several regional differences among 31P metabolites and pH in the AD risk group including elevated PCr/α-ATP, depressed PME/PDE, and elevated pH in the temporal cortices. Increased PCr/α-ATP throughout the brain was associated with aging. ConclusionsPhosphorus spectroscopy in the brain can be performed with high repeatability. Phosphorus metabolism varies with region and age, and is related to glucose uptake in adults at risk for AD. Phosphorus spectroscopy may be a valuable approach to study early changes in brain energetics in high-risk populations.

Emerging Role for 7T MRI and Metabolic Imaging for Pancreatic and Liver Cancer.

Advances in magnet technologies have led to next generation 7T magnetic resonance scanners which can fit in the footprint and price point of conventional hospital scanners (1.5–3T). It is therefore worth asking if there is a role for 7T magnetic resonance imaging and spectroscopy for the treatment of solid tumor cancers. Herein, we survey the medical literature to evaluate the unmet clinical needs for patients with pancreatic and hepatic cancer, and the potential of ultra-high field proton imaging and phosphorus spectroscopy to fulfil those needs. We draw on clinical literature, preclinical data, nuclear magnetic resonance spectroscopic data of human derived samples, and the efforts to date with 7T imaging and phosphorus spectroscopy. At 7T, the imaging capabilities approach histological resolution. The spectral and spatial resolution enhancements at high field for phospholipid spectroscopy have the potential to reduce the number of exploratory surgeries due to tumor boundaries undefined at conventional field strengths. Phosphorus metabolic imaging at 7T magnetic field strength, is already a mainstay in preclinical models for molecular phenotyping, energetic status evaluation, dosimetry, and assessing treatment response for both pancreatic and liver cancers. Metabolic imaging of primary tumors and lymph nodes may provide powerful metrics to aid staging and treatment response. As tumor tissues contain extreme levels of phospholipid metabolites compared to the background signal, even spectroscopic volumes containing less than 50% tumor can be detected and/or monitored. Phosphorus spectroscopy allows non-invasive pH measurements, indicating hypoxia, as a predictor of patients likely to recur. We conclude that 7T multiparametric approaches that include metabolic imaging with phosphorus spectroscopy have the potential to meet the unmet needs of non-invasive location-specific treatment monitoring, lymph node staging, and the reduction in unnecessary surgeries for patients undergoing resections for pancreatic cancer. There is also potential for the use of 7T phosphorous spectra for the phenotyping of tumor subtypes and even early diagnosis (<2 mL). Whether or not 7T can be used for all patients within the next decade, the technology is likely to speed up the translation of new therapeutics.

Energetic Basis for Exercise-Induced Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction.

Transient pulmonary congestion during exercise is emerging as an important determinant of reduced exercise capacity in heart failure with preserved ejection fraction (HFpEF). We sought to determine whether an abnormal cardiac energetic state underpins this process. We recruited patients across the spectrum of diastolic dysfunction and HFpEF (controls, n=11; type 2 diabetes, n=9; HFpEF, n=14; and severe diastolic dysfunction attributable to cardiac amyloidosis, n=9). Cardiac energetics were measured using phosphorus spectroscopy to define the myocardial phosphocreatine to ATP ratio. Cardiac function was assessed by cardiovascular magnetic resonance cine imaging and echocardiography and lung water using magnetic resonance proton density mapping. Studies were performed at rest and during submaximal exercise using a magnetic resonance imaging ergometer. Paralleling the stepwise decline in diastolic function across the groups (E/e' ratio; P<0.001) was an increase in NT-proBNP (N-terminal pro-brain natriuretic peptide; P<0.001) and a reduction in phosphocreatine/ATP ratio (control, 2.15 [2.09, 2.29]; type 2 diabetes, 1.71 [1.61, 1.91]; HFpEF, 1.66 [1.44, 1.89]; cardiac amyloidosis, 1.30 [1.16, 1.53]; P<0.001). During 20-W exercise, lower left ventricular diastolic filling rates (r=0.58; P<0.001), lower left ventricular diastolic reserve (r=0.55; P<0.001), left atrial dilatation (r=-0.52; P<0.001), lower right ventricular contractile reserve (right ventricular ejection fraction change, r=0.57; P<0.001), and right atrial dilation (r=-0.71; P<0.001) were all linked to lower phosphocreatine/ATP ratio. Along with these changes, pulmonary proton density mapping revealed transient pulmonary congestion in patients with HFpEF (+4.4% [0.5, 6.4]; P=0.002) and cardiac amyloidosis (+6.4% [3.3, 10.0]; P=0.004), which was not seen in healthy controls (-0.1% [-1.9, 2.1]; P=0.89) or type 2 diabetes without HFpEF (+0.8% [-1.7, 1.9]; P=0.82). The development of exercise-induced pulmonary congestion was associated with lower phosphocreatine/ATP ratio (r=-0.43; P=0.004). A gradient of myocardial energetic deficit exists across the spectrum of HFpEF. Even at low workload, this energetic deficit is related to markedly abnormal exercise responses in all 4 cardiac chambers, which is associated with detectable pulmonary congestion. The findings support an energetic basis for transient pulmonary congestion in HFpEF.

Use of cardiac magnetic resonance to detect changes in metabolism in heart failure.

The heart has a massive adenosine triphosphate (ATP) requirement, produced from the oxidation of metabolic substrates such as fat and glucose. Magnetic resonance spectroscopy offers a unique opportunity to probe this biochemistry: 31Phosphorus spectroscopy can demonstrate the production of ATP and quantify levels of the transport molecule phosphocreatine while 13Carbon spectroscopy can demonstrate the metabolic fates of glucose in real time. These techniques allow the metabolic deficits in heart failure to be interrogated and can be a potential future clinical tool.

Inherently decoupled 1 H antennas and 31 P loops for metabolic imaging of liver metastasis at 7 T.

High field 31 P spectroscopy has thus far been limited to diffuse liver disease. Unlike lower field-strength scanners, there is no body coil in the bore of the 7 T and despite inadequate penetration depth (<10 cm), surface coils are the current state-of-the-art for acquiring anatomical images to support multinuclear studies. We present a system of proton antennas and phosphorus loops for 31 P spectroscopy and provide the first ultrahigh-field phosphorus metabolic imaging of a tumor in the abdomen. Herein we characterize the degree to which antennas are isolated from underlying loops. Next, we evaluate the penetration depth of the two antennas available during multinuclear examinations. Finally, we combine phosphorus spectroscopy (two loops) with parallel transmit imaging (eight antennas) in a patient. The loops and antennas are inherently decoupled (no added circuitry, <0.1% power coupling). The penetration depth of two antennas gives twice that of conventional loops. The liver and full axial slice of the abdomen were imaged with eight transmit/receive antennas using parallel transmit B1-shimming to overcome image voids. Phosphorus spectroscopy from a liver metastasis resolved individual peaks for phosphocholine and phosphoethenalomine. Proton antennas are inherently decoupled from phosphorus loops. By using two proton antennas it is possible to perform region-of-interest image-based shimming in over 80% of the liver volume, thereby enabling phosphorus spectroscopy of localized disease. Shimming of the full extent of the abdominal cross-section is feasible using a parallel transmit array of eight antennas. A system architecture capable of supporting eight-channel parallel transmit and multinuclear spectroscopy is optimal for supporting multiparametric body imaging, including metabolic imaging, for monitoring the response of patients with liver metastases to cancer treatments and for patient risk stratification. In the meantime, the existing infrastructure using two antennas is sufficient for preliminary studies in metabolic imaging of tumors in the liver.

The pH sensitivity of APT-CEST using phosphorus spectroscopy as a reference method.

The pH value is a potential physiological marker for clinical diagnosis as it is altered in pathologies such as tumors. While intracellular pH can be measured noninvasively via phosphorus spectroscopy (31 P MRSI), Amide Proton Transfer-Chemical Exchange Saturation Transfer (APT-CEST) MRI has been suggested as an alternative method for pH quantification. To assess the suitability of APT-CEST contrast for pH quantification, two approaches (magnetization transfer ratio asymmetry [MTRasym ] and Lorentzian difference analysis [LDA]) for analyzing the Z-spectrum have been correlated with pH values obtained by 31 P MRSI. Fourteen patients with glioblastoma and 12 healthy controls were included. In contrast to MTRasym , the LDA is modeling the direct water saturation and the semi-solid magnetization transfer, allowing a separate evaluation of the aliphatic nuclear Overhauser effect and the APT-CEST. The results of our study show that the pH values obtained by 31 P MRSI correspond well with both methods describing the APT-CEST contrast. Two-sample t-test showed significant differences in MTRasym , LDA and pH obtained by 31 P MRSI for regions of interest in glioblastoma, contralateral control areas and normal appearing white matter (P<0.001). A slightly improved correlation between the amide signal and pH was found after performing LDA (r=0.78) compared with MTRasym (r=0.70). While both methods can be used to monitor pH changes, the LDA approach appears to be better suited.

Feasibility of absolute quantification for 31 P MRS at 7 T.

PurposePhosphorus spectroscopy can differentiate among liver disease stages and types. To quantify absolute concentrations of phosphorus metabolites, sensitivity calibration and transmit field (B1+) correction are required. The trend toward ultrahigh fields (7 T) and the use of multichannel RF coils makes this ever more challenging. We investigated the constraints on reference phantoms, and implemented techniques for the absolute quantification of human liver phosphorus spectra acquired using a 10‐cm loop and a 16‐channel array at 7 T.MethodsThe effect of phantom conductivity was assessed at 25.8 MHz (1.5 T), 49.9 MHz (3 T), and 120.3 MHz (7 T) by electromagnetic modeling. Radiofrequency field maps (B1±) were measured in phosphate phantoms (18 mM and 40 mM) at 7 T. These maps were used to assess the correction of 4 phantom 3D‐CSI data sets using 3 techniques: phantom replacement, explicit normalization, and simplified normalization. In vivo liver spectra acquired with a 10‐cm loop were corrected with all 3 methods. Simplified normalization was applied to in vivo 16‐channel array data sets.ResultsSimulations show that quantification errors of less than 3% are achievable using a uniform electrolyte phantom with a conductivity of 0.23‐0.86 S.m−1 at 1.5 T, 0.39‐0.58 S.m−1 at 3 T, and 0.34‐0.42 S.m−1 (16‐19 mM KH2PO4(aq)) at 7 T. The mean γ‐ATP concentration quantified in vivo at 7 T was 1.39 ± 0.30 mmol.L−1 to 1.71 ± 0.35 mmol.L−1 wet tissue for the 10‐cm loop and 1.88 ± 0.25 mmol.L−1 wet tissue for the array.ConclusionIt is essential to select a calibration phantom with appropriate conductivity for quantitative phosphorus spectroscopy at 7 T. Using an 18‐mM phosphate phantom and simplified normalization, human liver phosphate metabolite concentrations were successfully quantified at 7 T.

Phosphorus spectroscopy in acute TBI demonstrates metabolic changes that relate to outcome in the presence of normal structural MRI

Metabolic dysfunction is a key pathophysiological process in the acute phase of traumatic brain injury (TBI). Although changes in brain glucose metabolism and extracellular lactate/pyruvate ratio are well known, it was hitherto unknown whether these translate to downstream changes in ATP metabolism and intracellular pH. We have performed the first clinical voxel-based in vivo phosphorus magnetic resonance spectroscopy (31P MRS) in 13 acute-phase major TBI patients versus 10 healthy controls (HCs), at 3T, focusing on eight central 2.5 × 2.5 × 2.5 cm3 voxels per subject. PCr/γATP ratio (a measure of energy status) in TBI patients was significantly higher (median = 1.09) than that of HCs (median = 0.93) (p < 0.0001), due to changes in both PCr and ATP. There was no significant difference in PCr/γATP between TBI patients with favourable and unfavourable outcome. Cerebral intracellular pH of TBI patients was significantly higher (median = 7.04) than that of HCs (median = 7.00) (p = 0.04). Alkalosis was limited to patients with unfavourable outcome (median = 7.07) (p < 0.0001). These changes persisted after excluding voxels with > 5% radiologically visible injury. This is the first clinical demonstration of brain alkalosis and elevated PCr/γATP ratio acutely after major TBI. 31P MRS has potential for non-invasively assessing brain injury in the absence of structural injury, predicting outcome and monitoring therapy response.

Study on denervated rat skeletal muscle by 7.0 T 31P-MR phosphorus spectroscopy

Objective To investigate the changes of 31P-MRS in denervated skeletal muscle at 7.0 T MR system. Methods In the experiment group, a total of 18 male Sprague-Dawley rats aged 6-8 weeks old and weighing 200-250 g were obtained. The right posterior femoral nerve were transected, and the proximal stumps were ligated by using 5-0 nylon stitches to preclude spontaneous repair. A sham surgery (incision and exploration of the nerve) was performed at the same time (n=6). Before rat model established and at varying times after initial surgery (3 d, and 1, 2, 4, 6, and 8 weeks). 31P-MR spectra of rat quadriceps femoris were acquired on 7.0 T Agilent small animal MR imaging system. We quantified the phosphocreatine (PCr), adenosine triphosphate(β-ATP), and inorganic phosphate (Pi) using Creatine phosphate disodium salt(10 mmol/L) as an external standard. The ratios, include PCr/Pi, Pi/β-ATP, PCr/β-ATP, PCr/(PCr+Pi) and Pi/(PCr+Pi) were quantified in jMRUI. All data were analyzed by one way analysis of variance (ANOVA) with posttest inter-group comparisons using Bonferroni test. Comparative analysis methods between the experimental and control group were performed via independent samples t test. P<0.05 was considered as statistically significance. Results The average measured concentrations of β-ATP, PCr, and Pi in control groups were (6.654±0.178) μmol/g, (25.656±0.738) μmol/g, and (1.594±0.096) μmol/g, respectively. There were significant statistically differences in β-ATP, PCr, Pi, PCr/Pi, PCr/PCr+Pi,Pi/PCr+Pi between the study and control group(P<0.05) at any measurement time point after denervation. Pi/β-ATP,PCr/β-ATP and pHi in the experimental group significantly statistically differed from those of the control group (all P<0.05)at each time point except on day 3 after operation. The total concentrations of β-ATP and PCr were reduced by 11.5% and 19.7% respectively on day 3. Thereafter, β-ATP and PCr declined rapidly by 63.1% and 68.8% at week 4 respectively, then decreased slowely by 74.0%和82.3% till week 10. The change of PCr/Pi is similar to β-ATP and PCr, but more remarkable. Pi, Pi/PCr+Pi, Pi/ATP showed a progressively increase till week 10. The intra-cellular pH (pHi) of normal rat muscles was 7.033±0.017, While the pHi gently in experiment rat muscles decreased during the entire experiment. Conclusion 31P-MRS with 7.0 T can quantify the temporal changes of energy metabolism and pHi in normal and denervated rat muscles. It shows that the dysfunction of energy metabolism are progressive with time and that they begin within a short period following the nerve section, the change of β-ATP, PCr, PCr/Pi take place primarily within 4 weeks after denervation. β-ATP, PCr, and PCr/Pi may be potential biomarkers of energy metabolism in the evaluation of denervated muscle atrophy. Key words: Magnetic resonance spectroscopy; Muscular disorders, atrophic; Denervation; Energy metabolism; Intracellular pH

Preoperative indication for systemic therapy extended to patients with early-stage breast cancer using multiparametric 7-tesla breast MRI.

PurposeTo establish a preoperative decision model for accurate indication of systemic therapy in early-stage breast cancer using multiparametric MRI at 7-tesla field strength.Materials and methodsPatients eligible for breast-conserving therapy were consecutively included. Patients underwent conventional diagnostic workup and one preoperative multiparametric 7-tesla breast MRI. The postoperative (gold standard) indication for systemic therapy was established from resected tumor and lymph-node tissue, based on 10-year risk-estimates of breast cancer mortality and relapse using Adjuvant! Online. Preoperative indication was estimated using similar guidelines, but from conventional diagnostic workup. Agreement was established between preoperative and postoperative indication, and MRI-characteristics used to improve agreement. MRI-characteristics included phospomonoester/phosphodiester (PME/PDE) ratio on 31-phosphorus spectroscopy (31P-MRS), apparent diffusion coefficients on diffusion-weighted imaging, and tumor size on dynamic contrast-enhanced (DCE)-MRI. A decision model was built to estimate the postoperative indication from preoperatively available data.ResultsWe included 46 women (age: 43-74yrs) with 48 invasive carcinomas. Postoperatively, 20 patients (43%) had positive, and 26 patients (57%) negative indication for systemic therapy. Using conventional workup, positive preoperative indication agreed excellently with positive postoperative indication (N = 8/8; 100%). Negative preoperative indication was correct in only 26/38 (68%) patients. However, 31P-MRS score (p = 0.030) and tumor size (p = 0.002) were associated with the postoperative indication. The decision model shows that negative indication is correct in 21/22 (96%) patients when exempting tumors larger than 2.0cm on DCE-MRI or with PME>PDE ratios at 31P-MRS.ConclusionsPreoperatively, positive indication for systemic therapy is highly accurate. Negative indication is highly accurate (96%) for tumors sized ≤2,0cm on DCE-MRI and with PME≤PDE ratios on 31P-MRS.

FV 6 Sustained GABA reduction induced by anodal Transcranial direct current stimulation (tDCS) in motor cortex – a proton magnetic resonance spectroscopy study

Background Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates excitability of neurons in the cerebral cortex. Anodal tDCS has been reported to modulate the activation of motor cortex as well as GABA concentration in motor cortex ( Nitsche and Paulus, 2000 ). Objective To date very little is known about the nature and duration of tDCS induced effects. We aimed to investigate long-term effects of anodal tDCS on the primary motor cortex (M1). Repeated magnetic resonance spectroscopy (MRS) was employed to measure relative gamma-aminobutyric acid concentrations in M1 up to 60 min after stimulation. Materials and methods Twenty right-handed healthy volunteers were recruited in RWTH Aachen University. 1 mA anodal and sham tDCS were applied for 10 min, respectively. MRS scans were performed before and after stimulation on a 3T Siemens PRISMA whole-body scanner, GABA-edited spectra were acquired from a volume of interest of 3 × 3 × 3 cm (27 mL) carefully placed on the hand area of the left M1 ( Fig. 1 ). MEGA-PRESS J-editing ( Mescher et al., 1998 ) was used for GABA detection. Data processing and quantification of spectra was performed with TARQUIN ( Wilson et al., 2011 ). Results An ANOVA was performed on GABA concentrations with stimulation (sham vs. anodal) and measurement (12 measurements: 2 pre-stimulation and 10 post-stimulation measurements) as between- and within-participants factors, respectively. The main effects of stimulation and measurements were significant F (1, 18) = 9.200, p = .007 and F (11, 198) = 2.354, p = .010. Crucially, the interaction was significant F (11, 198) = 3.089, p Fig. 2 ). In other words, GABA signal showed no change over time in the sham group, whereas it decreased significantly in the anodal group and stayed at about the same level across the whole planned test measurements over 86 min. Discussion and conclusion Such a long-lasting (over 86 min) decrease in GABA concentration corresponds not only to the reported behavioral effects of tDCS stimulation, such as increased motor learning capacity, but also, to the timeline of increased brain energy consumption following anodal tDCS as measured with Phosphorus spectroscopy ( Binkofski et al., 2011 ). Our results are relevant for the understanding of the mechanism of motor cortical plasticity and neuropsychiatric diseases in humans.

Multiparametric and molecular imaging of breast tumors with MRI and PET/MRI

Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity. Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ((1)H-MRSI) as well as combinations of radiological and MRI techniques (e. g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG). Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7T). Emerging parameters comprise novel promising techniques, such as sodium imaging ((23)Na MRI), phosphorus spectroscopy ((31)P-MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level-dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers. Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer.

Multiparametric MRI With Dynamic Contrast Enhancement, Diffusion-Weighted Imaging, and 31-Phosphorus Spectroscopy at 7 T for Characterization of Breast Cancer.

To describe and to correlate tumor characteristics on multiparametric 7 tesla (T) breast magnetic resonance imaging (MRI) with prognostic characteristics from postoperative histopathology in patients with breast cancer. Institutional review board approval and written informed consent of 15 women (46-70 years) with 17 malignant lesions were obtained. In this prospective study (March 2013 to March 2014), women were preoperatively scanned using dynamic contrast-enhanced MRI, diffusion-weighted imaging, and 31-phosphorus spectroscopy (¹³P-MRS). The value of the protocol was assessed to quantify tumor differentiation and proliferation. Dynamic contrast-enhanced MRI was assessed according to the American College of Radiology Breast Imaging Reporting and Data System-MRI lexicon. Apparent diffusion coefficients (ADCs) were calculated from diffusion-weighted imaging. On ¹³P-MRS, at the location of the tumor, the amount of phosphorus components was obtained in a localized spectrum. In this spectrum, the height of phosphodiester (PDE) and phosphomonoester (PME) peaks was assessed to serve as a measure for metabolic activity, stratifying tumors into a PDE > PME, PDE = PME, or PDE < PME group. Tumor grade and mitotic count from resection specimen were compared with the MRI characteristics using explorative analyses. On dynamic contrast-enhanced MRI, the mean tumor size was 24 mm (range, 6-55 mm). An inverse trend was seen between ADC and tumor grade (P = 0.083), with mean ADC of 867 × 10⁻⁶ mm²/s for grade 1 (N = 4), 751 × 10⁻⁶ mm²/s for grade 2 (N = 6), and 659 × 10⁻⁶ mm²/s for grade 3 (N = 2) tumors. Between P-MR spectra and mitotic count, a relative increase of PME over PDE showed significant association with increasing mitotic counts (P = 0.02); a mean mitotic count of 6 was found in the PDE greater than PME group (N = 7), 8 in the PDE = PME group (N = 1), and 17 in the PDE < PME group (N = 3). Multiparametric 7 T breast MRI is feasible in clinical setting and shows association between ADC and tumor grade, and between ¹³P-MRS and mitotic count.

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia.

Functional imaging of the musculoskeletal system.

Functional imaging, which provides information of how tissues function rather than structural information, is well established in neuro- and cardiac imaging. Many musculoskeletal structures, such as ligaments, fascia and mineralized bone, have by definition a mainly structural role and clearly don't have the same functional capacity as the brain, heart, liver or kidney. The main functionally responsive musculoskeletal tissues are the bone marrow, muscle and nerve and, as such, magnetic resonance (MR) functional imaging has primarily addressed these areas. Proton or phosphorus spectroscopy, other fat quantification techniques, perfusion imaging, BOLD imaging, diffusion and diffusion tensor imaging (DTI) are the main functional techniques applied. The application of these techniques in the musculoskeletal system has mainly been research orientated where they have already greatly enhanced our understanding of marrow physiology, muscle physiology and neural function. Going forwards, they will have a greater clinical impact helping to bridge the disconnect often seen between structural appearances and clinical symptoms, allowing a greater understanding of disease processes and earlier recognition of disease, improving prognostic prediction and optimizing the monitoring of treatment effect.

Molekulare Brustbildgebung

The aim of molecular imaging is to visualize and quantify biological, physiological and pathological processes at cellular and molecular levels. Molecular imaging using various techniques has recently become established in breast imaging. Currently molecular imaging techniques comprise multiparametric magnetic resonance imaging (MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), proton MR spectroscopy ((1)H-MRSI), nuclear imaging by breast-specific gamma imaging (BSGI), positron emission tomography (PET) and positron emission mammography (PEM) and combinations of techniques (e.g. PET-CT and multiparametric PET-MRI). Recently, novel techniques for molecular imaging of breast tumors, such as sodium imaging ((23)Na-MRI), phosphorus spectroscopy ((31)P-MRSI) and hyperpolarized MRI as well as specific radiotracers have been developed and are currently under investigation. It can be expected that molecular imaging of breast tumors will enable a simultaneous assessment of the multiple metabolic and molecular processes involved in cancer development and thus an improved detection, characterization, staging and monitoring of response to treatment will become possible.