Unveiling a hidden <sup>31</sup>P signal coresonating with extracellular inorganic phosphate by outer‐volume‐suppression and localized <sup>31</sup>P MRS in the human brain at 7T

Ren, Jimin; Shang, Ty; Sherry, A. Dean; Malloy, Craig R.

doi:10.1002/mrm.27121

Cited by 22 publications

(65 citation statements)

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“…The second study specifically targets the downfield Pi peak and shows the influences of the blood and CSF pool on this peak. 36 Although we have assigned the downfield Pi peak as mitochondrial Pi, it is expected to be composed of several other compounds as well. For instance, 2,3-DPG is highly abundant in blood and expresses itself at 7 T as two peaks in close proximity to the resonance of Pi and phosphocholine (PC).…”

Section: Discussionmentioning

confidence: 96%

“…Two recent studies have been published that include high SNR 31 P MRSI protocols at 7 T. The first study does not observe any change in high‐energy phosphates due to a visual stimulation, but on the other hand does not include the downfield Pi peak in their analysis. The second study specifically targets the downfield Pi peak and shows the influences of the blood and CSF pool on this peak …”

Section: Discussionmentioning

confidence: 99%

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SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

et al. 2019

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SummaryEnergy metabolism of the human visual cortex was investigated by performing 31P functional MRS.IntroductionThe human brain is known to be the main glucose demanding organ of the human body and neuronal activity can increase this energy demand. In this study we investigate whether alterations in pH during activation of the brain can be observed with MRS, focusing on the mitochondrial inorganic phosphate (Pi) pool as potential marker of energy demand.MethodsSix participants were scanned with 16 consecutive 31P‐MRSI scans, which were divided in 4 blocks of 8:36 minutes of either rest or visual stimulation. Since the signals from the mitochondrial compartments of Pi are low, multiple approaches to achieve high SNR 31P measurements were combined. This included: a close fitting 31P RF coil, a 7 T‐field strength, Ernst angle acquisitions and a stimulus with a large visual angle allowing large spectroscopy volumes containing activated tissue.ResultsThe targeted resonance downfield of the main Pi peak could be distinguished, indicating the high SNR of the 31P spectra. The peak downfield of the main Pi peak is believed to be connected to mitochondrial performance. In addition, a BOLD effect in the PCr signal was observed as a signal increase of 2–3% during visual stimulation as compared to rest. When averaging data over multiple volunteers, a small subtle shift of about 0.1 ppm of the downfield Pi peak towards the main Pi peak could be observed in the first 4 minutes of visual stimulation, but no longer in the 4 to 8 minute scan window. Indications of a subtle shift during visual stimulation were found, but this effect remains small and should be further validated.ConclusionOverall, the downfield peak of Pi could be observed, revealing opportunities and considerations to measure specific acidity (pH) effects in the human visual cortex.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

et al. 2019

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“…Another methodological contribution of this study was the resolution of Pi into two separate peaks, intracellular and extracellular compartments ( Ren et al, 2018 ). The extracellular Pi pool includes the signal of Pi from both the vascular and interstitial space plus the space occupied by cerebrospinal fluid (CSF).…”

Section: Discussionmentioning

confidence: 99%

“…Total-ATP (t-ATP) was calculated by averaging the α-, β-, and γ-ATP resonances. The brain 31 P spectra revealed two distinct peaks for Pi, assigned intra-and extracellular Pi, the latter including contributions from both interstitial and intravascular spaces (Ren et al, 2018). For the membrane phospholipid metabolite index, phosphomonoesters (PMEs) were calculated by summation of PE and PC, whereas phosphodiesters were by summation of GPE and GPC.…”

Section: P Mrs Data Analysismentioning

confidence: 99%

“…This capability was previously limited due to the use and insensitivity of lower magnetic strengths such as 1.5-Tesla (Smith et al, 1995;Lotti et al, 1996;Forlenza et al, 2005) or 3-Tesla (Mandal et al, 2012;Rijpma et al, 2018). Another methodological contribution of this study was the resolution of Pi into two separate peaks, intracellular and extracellular compartments (Ren et al, 2018). The extracellular Pi pool includes the signal of Pi from both the vascular and interstitial space plus the space occupied by cerebrospinal fluid (CSF).…”

Section: Population Of Interestmentioning

confidence: 99%

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Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment

Das

Ren

Spence

et al. 2020

Front. Aging Neurosci.

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Background: The human brain has high energy requirements that continuously support healthy neuronal activity and cognition. A disruption in brain energy metabolism (BEM) may contribute to early neuropathological changes such as accumulation of β-amyloid and tau in vulnerable populations. One such population is amnestic mild cognitive impairment (aMCI) where some individuals are at risk for developing dementia, i.e. Alzheimer's disease (AD). Recent advances in imaging technology are providing new avenues to measure BEM accurately using 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7-Tesla. This study investigates whether a methodology using partial volume-coil 31P MRS at 7T over parieto-occipital lobes can accurately quantify high-energy phosphate and membrane phospholipid metabolites in aMCI. A secondary objective was to explore BEM and membrane phospholipid indices' correspondence with cognitive performance in domains of executive function (EF), memory, attention, and visuospatial skills in aMCI, a heterogeneous population. Methods: 19 aMCI participants enrolled in the study completed cognitive assessment and 31P MRS scan. BEM indices were measured using three energy indicators: energy reserve (PCr/t-ATP), energy consumption (intracellular_Pi/t-ATP), and metabolic state (PCr/intracellular_Pi) along with regulatory co-factors of BEM-intracellular Mg 2+ and pH; whereas the ratio of phosphomonoesters (PMEs) to phosphodiesters (PDEs)membrane phospholipid indicator. Results: 31P MRS scan showed thirteen well-resolved peaks with precise quantification of the phosphorus metabolites at UHF. The higher BEM indices were associated with lower cognitive performance of memory [(energy reserve indicator: CVLT p = 0.004), (metabolic state indicator: CVLT p = 0.007)], executive function [(metabolic state indicator: TOSL (p = 0.044)], and attention [(pH: selective auditory task, p = 0.044)]. The finding of an inverse relationship observed in the parieto-occipital lobes suggests an association between neuronal energy markers with cognition in aMCI.

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Volumetric mapping of intra‐ and extracellular pH in the human brain using ³¹P MRSI at 7T

Korzowski

Weinfurtner

Mueller

et al. 2020

Magnetic Resonance in Med

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Purpose In vivo 31P MRSI enables noninvasive mapping of absolute pH values via the pH‐dependent chemical shifts of inorganic phosphates (Pi). A particular challenge is the quantification of extracellular Pi with low SNR in vivo. The purpose of this study was to demonstrate feasibility of assessing both intra‐ and extracellular pH across the whole human brain via volumetric 31P MRSI at 7T. Methods 3D 31P MRSI data sets of the brain were acquired from three healthy volunteers and three glioma patients. Low‐rank denoising was applied to enhance the SNR of 31P MRSI data sets that enables detection of extracellular Pi at high spatial resolutions. A robust two‐compartment quantification model for intra‐ and extracellular Pi signals was implemented. Results In particular low‐rank denoising enabled volumetric mapping of intra‐ and extracellular pH in the human brain with voxel sizes of 5.7 mL. The average intra‐ and extracellular pH measured in white matter of healthy volunteers were 7.00 ± 0.00 and 7.33 ± 0.03, respectively. In tumor tissue of glioma patients, both the average intra‐ and extracellular pH increased to 7.12 ± 0.01 and 7.44 ± 0.01, respectively, compared to normal appearing tissue. Conclusion Mapping of pH values via 31P MRSI at 7T using the proposed two‐compartment quantification model improves reliability of pH values obtained in vivo, and has the potential to provide novel insights into the pH heterogeneity of various tissues.

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Unveiling a hidden ³¹P signal coresonating with extracellular inorganic phosphate by outer‐volume‐suppression and localized ³¹P MRS in the human brain at 7T

Cited by 22 publications

References 40 publications

SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment

Volumetric mapping of intra‐ and extracellular pH in the human brain using ³¹P MRSI at 7T

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Unveiling a hidden 31P signal coresonating with extracellular inorganic phosphate by outer‐volume‐suppression and localized 31P MRS in the human brain at 7T

Cited by 22 publications

References 40 publications

SNR optimized 31P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

SNR optimized 31P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

Relationship of Parieto-Occipital Brain Energy Phosphate Metabolism and Cognition Using 31P MRS at 7-Tesla in Amnestic Mild Cognitive Impairment

Volumetric mapping of intra‐ and extracellular pH in the human brain using 31P MRSI at 7T

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Unveiling a hidden ³¹P signal coresonating with extracellular inorganic phosphate by outer‐volume‐suppression and localized ³¹P MRS in the human brain at 7T

SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

SNR optimized ³¹P functional MRS to detect mitochondrial and extracellular pH change during visual stimulation

Volumetric mapping of intra‐ and extracellular pH in the human brain using ³¹P MRSI at 7T